Hyponatremia

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Hyponatremia
Classification and external resources
Na-TableImage.png
ICD-10 E87.1
ICD-9 276.1
DiseasesDB 6483
MedlinePlus 000394
eMedicine emerg/275 med/1130 ped/1124
Patient UK Hyponatremia
MeSH D007010

Hyponatremia (American English) or hyponatraemia (British English) is defined as a low sodium concentration in the blood. In most cases, it is caused by drinking too much water, resulting in an electrolyte disturbance in which the sodium ion concentration in the blood plasma is lower than normal.[1] Too little sodium in the diet alone is very rarely the cause of hyponatremia, although it can promote hyponatremia indirectly and has been associated with Ecstasy-induced hyponatremia.[2] Sodium loss can lead to a state of low blood volume, which serves as a signal for the release of anti-diuretic hormone (ADH).[citation needed] ADH release leads to water retention and dilution of the blood resulting in a low sodium concentration.

Exercise-associated hyponatremia (EAH) is common in marathon runners and participants of other endurance events.[3] 13% of the athletes who finished the 2002 Boston Marathon were in a hyponatremic state, i.e. their salt levels in their blood had fallen below an acceptable level.[citation needed]

Sodium is the primary positively charged ion in the environment outside of the cell and cannot freely cross from the interstitial space into the cell. Charged sodium ions attract up to 25 water molecules around them thereby creating a large polar structure that is too large to pass through the cell membrane. Normal serum sodium levels are between approximately 135 and 145 mEq/liter (135 - 145 mmol/L). Hyponatremia is generally defined as a serum sodium level of less than 135 mEq/L and is considered severe when the serum sodium level is below 125 mEq/L.[4][5]

Many conditions including congestive heart failure, liver failure, kidney failure and pneumonia are commonly associated with a low sodium concentration in the blood. This state can also be caused by overhydration from drinking too much water due to excess thirst (polydipsia).

Signs and symptoms[edit]

Signs and symptoms of hyponatremia include nausea and vomiting, headache, short-term memory loss, confusion, lethargy, fatigue, loss of appetite, restlessness, irritability, muscle weakness, spasms or cramps, seizures, and decreased consciousness or coma.[6] The presence and severity of signs and symptoms are associated with the level of plasma sodium (salt level in the blood), with the lowest levels of plasma sodium associated with more severe symptoms (the lower the sodium concentration the more severe the signs/symptoms). However, emerging data suggest that mild hyponatremia (plasma sodium levels at 131 mEq/L or above) is associated with numerous complications or subtle, presently unrecognized symptoms[7] (e.g., increased falls, altered posture and gait, reduced attention).[8]

Neurological (brain) symptoms typically occur with very low levels of plasma sodium (usually <115 mEq/L).[6] When sodium levels in the blood become very low, water enters the brain cells and causes them to swell. This results in increased pressure in the skull and causes hyponatremic encephalopathy. As the pressure increases in the skull, herniation of the brain can occur which is a squeezing of the brain across the internal structures of the skull. This can lead to headache, nausea, vomiting, confusion, seizures, brain stem compression and respiratory arrest (stopping breathing), and non-cardiogenic accumulation of fluid in the lungs.[9] This is usually fatal if not immediately treated.

Symptom severity depends on how fast and how severe the drop in blood salt level. A gradual drop, even to very low levels, may be tolerated well if it occurs over several days or weeks, because of neuronal adaptation. The presence of underlying neurological disease such as a seizure disorder or non-neurological metabolic abnormalities, also affects the severity of neurologic symptoms.

Causes[edit]

Based on the above classification, some of the many specific causes of hyponatremia can be listed as follows:

Hypervolemic hyponatremia —Both sodium & water content increase: Increase in sodium content leads to hypervolemia and water content to hyponatremia. Total body water and sodium are regulated independently.[10]

Euvolemic hyponatremia — there is volume expansion in the body, no edema, but hyponatremia occurs [10]

  • states of severe pain or nausea
  • in the setting of trauma or other damage to the brain
  • SIADH (and its many causes)
  • Hypothyroidism
  • Glucocorticoid (steroid) deficiency

Hypovolemic hyponatremia — The hypovolemia (extracellular volume loss) is due to total body sodium loss. The hyponatremia is caused by a relatively smaller loss in total body water.[10]

Miscellaneous causes of hyponatremia that are not included under the above classification scheme include the following:

A prolonged period of exercise may be a cause.[11]

Diagnosis[edit]

Examination includes taking vital signs when lying, sitting, and standing, and an assessment of how much blood is in the body. This determination (i.e. hypervolemic, euvolemic, hypovolemic) helps guide treatment decisions. A full assessment of other medical conditions (comorbidity) is also taken, because heart and brain conditions affect the results and the treatment decisions.

Pathophysiology[edit]

The hyponatremia can be spurious (false) and/or artifactual hyponatremia in which case there is no hypotonicity. Hypertonic hyponatremia, caused by resorption of water drawn by molecules such as glucose (hyperglycemia or diabetes) or mannitol (hypertonic infusion). Isotonic hyponatremia, more commonly called "pseudohyponatremia," is caused by measurement error due to high blood triglyceride level (most common) or paraproteinemia. It occurs when using techniques that measure the amount of sodium in a specified volume of serum/plasma, or that dilute the sample before analysis.[12]

True hyponatremia is Hypotonic hyponatremia and is by far the most common type, and is often simply referred to as "hyponatremia." Hypotonic hyponatremia is categorized in 3 ways based on the patient's blood volume status. Each category represents a different underlying reason for the increase in ADH that led to the water retention and thence hyponatremia:

  • Hypervolemic hyponatremia, wherein there is decreased effective circulating volume (less blood flowing in the body) even though total body volume is increased (by the presence of edema or swelling, especially in the ankles). The decreased effective circulating volume stimulates the release of anti-diurectic hormone(ADH), which in turn leads to water retention. Hypervolemic hyponatremia is most commonly the result of congestive heart failure, liver failure (cirrhosis), or kidney disease (nephrotic syndrome).
  • Euvolemic hyponatremia, wherein the increase in ADH is secondary to either physiologic but excessive ADH release (as occurs with nausea or severe pain) or inappropriate and non-physiologic secretion of ADH, i.e. syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH). Often categorized under euvolemic is hyponatremia due to inadequate urine solute (not enough chemicals or electrolytes to produce urine) as occurs in beer potomania or "tea and toast" hyponatremia, hyponatremia due to hypothyroidism or central adrenal insufficiency, and those rare instances of hyponatremia that are truly secondary to excess water intake (i.e., extreme psychogenic polydipsia)
  • Hypovolemic hyponatremia, wherein ADH secretion is stimulated by or associated with volume depletion (not enough water in the body).

The volemic classification fails to include spurious (false) and/or artifactual hyponatremia, which is addressed in the osmolar classification. This includes hyponatremia that occurs in the presence of massive hypertriglyceridemia, severe hyperglycemia, and extreme elevation of immunoglobulin levels.

In chronic hyponatremia, sodium (salt) levels drop gradually over several days or weeks and symptoms and complications are typically moderate. Chronic hyponatremia is often called asymptomatic hyponatremia in clinical settings because it is thought to have no symptoms; however, emerging data suggests that "asymptomatic" hyponatremia is not actually asymptomatic.[7]

In acute hyponatremia sodium (salt) levels drop rapidly, resulting in potentially dangerous effects, such as rapid brain swelling, which can result in coma and death.

Treatment[edit]

The treatment of hyponatremia depends on the underlying cause and whether the patient's blood volume status is hypervolemic, euvolemic, or hypovolemic. In the setting of hypovolemia, intravenous administration of normal saline (salt) is usual, care being taken not to raise the serum sodium level (salt level in the blood) too quickly (see below). Euvolemic hyponatremia is usually managed by fluid restriction and treatment to abolish any stimuli for ADH secretion such as nausea. Likewise, drugs causing SIADH are discontinued if possible. Patients with euvolemic hyponatremia that persists despite those measures may be candidates for a so-called vaptan drug as discussed below. Hypervolemic hyponatremia is usually treated by addressing the underlying heart or liver failure. If it is not possible to do so, the treatment becomes the same as that for euvolemic hyponatremia (i.e. fluid restriction and/or use of a vaptan drug).

Hyponatremia is corrected slowly in order to lessen the risk of the development of central pontine myelinolysis (CPM), a severe neurological disease involving a breakdown of the myelin sheaths covering parts of nerve cells. In fact, overly rapid correction of hyponatremia is the most common cause of that potentially devastating disorder.[13] During treatment of hyponatremia, the serum sodium (salt level in the blood) is not allowed to rise by more than 8 mmol/l over 24 hours (i.e. 0.33 mmol/l/h rate of rise). In practice, too rapid correction of hyponatremia and thence CPM is most likely to occur during the treatment of hypovolemic hyponatremia. In particular, once the hypovolemic state has been corrected, the signal for ADH release disappears. At that point, there will be an abrupt water diuresis (an increase in urination since there is no longer any ADH acting to retain the water). A rapid and profound rise in serum sodium (salt level in the blood) can then occur. Should the rate of rise of serum sodium exceed 0.33 mmol/l/h over several hours, vasopressin may be administered to prevent ongoing rapid water diuresis (excessive urination).[14]

Pharmaceutically, vasopressin receptor antagonists can be used in the treatment of hyponatremia, especially in patients with SIADH, congestive heart failure or liver cirrhosis. A vasopressin receptor antagonist is an agent that interferes with the action at the vasopressin receptors. A new class of medication, the "vaptan" drugs has been specifically developed to inhibit the action of vasopressin on its receptors (V1A, V1B, and V2). These receptors have a variety of functions, with the V1A and V2 receptors are expressed peripherally and involved in the modulation of blood pressure and kidney function respectively, while the V1A and V1B receptors are expressed in the central nervous system. V1A is expressed in many regions of the brain, and has been linked to a variety of social behaviors in humans and animals.

Vaptan drugs[edit]

The “vaptan” class of drugs contains a number of compounds with varying selectivity, several of which are either already in clinical use or in clinical trials as of 2010.

Unselective (mixed V1A, V2)

V1A selective

  • Relcovaptan

V1B selective

  • Nelivaptan

V2 selective

  • Mozavaptan
  • Satavaptan

The V2-receptor antagonists tolvaptan and conivaptan allow excretion of electrolyte free water and are effective in increasing serum sodium in euvolemic and hypervolemic hyponatremia.[15]

Complications[edit]

Chronic hyponatremia can lead to such complications as neurological impairments. These neurological impairments most often affect gait (walking) and attention, and can lead to falls, osteoporosis, and decreased reaction time.

Complications for chronic hyponatremia are most dangerous for geriatric patients. Falls are the leading cause of deaths related to injury among people 65 years or older. Recent work by Verbalis et al.[16] suggests that hyponatremia induces osteoporosis and found the adjusted odds ratio for developing osteoporosis to be 2.87 times higher among adults with mild hyponatremia compared to those without.

Acute hyponatremia can lead to much more serious complications including brain disease, brain herniation, cardiopulmonary arrest, cerebral edema (brain swelling), seizures, coma, and death.

Epidemiology[edit]

Hyponatremia is the most common electrolyte disorder. Electrolytes are sodium (salt), potassium, calcium, magnesium, chloride, hydrogen phosphate, and hydrogen carbonate. The disorder is more frequent in females, the elderly, and in people who are hospitalized. The incidence of hyponatremia depends largely on the patient population. A hospital incidence of 15–20% is common, while only 3–5% of people who are hospitalized have a serum sodium level (salt blood level) of less than 130 mEq/L. Hyponatremia has been reported in up to 30% of elderly patients in nursing homes and is also present in approximately 30% of depressed patients on selective serotonin reuptake inhibitors.[7]

See also[edit]

References[edit]

  1. ^ Reynolds, R. M; Padfield, PL; Seckl, JR (2006). "Disorders of sodium balance". BMJ 332 (7543): 702–5. doi:10.1136/bmj.332.7543.702. PMC 1410848. PMID 16565125. 
  2. ^ "High incidence of mild hyponatraemia in females using ecstasy at a rave party". 
  3. ^ Rosner, M. H.; Kirven, J. (2006). "Exercise-Associated Hyponatremia". Clinical Journal of the American Society of Nephrology 2 (1): 151–61. doi:10.2215/CJN.02730806. PMID 17699400. 
  4. ^ "Hyponatremia". MayoClinic.com. Retrieved 2010-09-01. 
  5. ^ "Hyponatremia". Medscape. Retrieved 2013-06-30. 
  6. ^ a b Babar, S. (October 2013). "SIADH Associated With Ciprofloxacin.". The Annals of Pharmacotherapy (Sage Publishing) 47 (10): 1359–1363. doi:10.1177/1060028013502457. ISSN 1060-0280. PMID 24259701. Retrieved November 18, 2013. 
  7. ^ a b c Schrier, Robert W. (2010). "Does 'asymptomatic hyponatremia' exist?". Nature Reviews Nephrology 6 (4): 185. doi:10.1038/nrneph.2010.21. PMID 20348927. 
  8. ^ Decaux, Guy (2006). "Is Asymptomatic Hyponatremia Really Asymptomatic?". The American Journal of Medicine 119 (7): S79–82. doi:10.1016/j.amjmed.2006.05.013. PMID 16843090. 
  9. ^ Moritz, M. L.; Ayus, J. C. (2003). "The pathophysiology and treatment of hyponatraemic encephalopathy: An update". Nephrology Dialysis Transplantation 18 (12): 2486–91. doi:10.1093/ndt/gfg394. PMID 14605269. 
  10. ^ a b c Mange, Kevin; Matsuura, D; Cizman, B; Soto, H; Ziyadeh, FN; Goldfarb, S; Neilson, EG (1997). "Language Guiding Therapy: The Case of Dehydration versus Volume Depletion". Annals of Internal Medicine 127 (9): 848–53. doi:10.7326/0003-4819-127-9-199711010-00020. PMID 9382413. 
  11. ^ Bennett, BL; Hew-Butler, T; Hoffman, MD; Rogers, IR; Rosner, MH (Sep 2013). "Wilderness Medical Society practice guidelines for treatment of exercise-associated hyponatremia.". Wilderness & environmental medicine 24 (3): 228–40. doi:10.1016/j.wem.2013.01.011. PMID 23590928. 
  12. ^ "What is pseudohyponatraemia?". American Association for Clinical Chemistry. Retrieved 16 September 2013. 
  13. ^ Bernsen HJ, Prick MJ (September 1999). "Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia". Acta Neurol Belg 99 (3): 189–93. PMID 10544728. 
  14. ^ Adrogué, Horacio J.; Madias, Nicolaos E. (2000). "Hyponatremia". New England Journal of Medicine 342 (21): 1581–9. doi:10.1056/NEJM200005253422107. PMID 10824078. 
  15. ^ Zenenberg, Robert; Carluccio, Alessia; Merlin, Mark (2010). "Hyponatremia: Evaluation and Management". Hospital Practice 38 (1): 89–96. doi:10.3810/hp.2010.02.283. PMID 20469629. 
  16. ^ Ayus, J. C.; Moritz, M. L. (2010). "Bone Disease as a New Complication of Hyponatremia: Moving Beyond Brain Injury". Clinical Journal of the American Society of Nephrology 5 (2): 167–8. doi:10.2215/CJN.09281209. PMID 20089487. 

External links[edit]