Sodium deficiency diseases

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What is sodium?
Sodium is an essential nutrient required for regulating blood volume and blood pressure in the human body.
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Sodium deficiency disease, medically termed as 'hyponatremia' results when the serum sodium (Na+) drops below optimum level of 135 mmol/L (mEq/L). It is a serious electrolyte imbalance with devastating effects on the cerebral function, if neglected. Serum Na+ levels suddenly dropping below 115 mEq/L is a very serious state of health and medical emergency.

Sodium deficiency diseases have multifactorial etiologies and may present multiple causes in the same patient. In some diseases, such as heart failure, hepatic cirrhosis, severe diarrhea, persistent vomiting, excessive thirst or renal salt-wasting, both sodium and water homeostasis go awry. This sodium or/and water imbalance may evolve into an emergency. The treatment may be required to be started before a confirmatory diagnosis. Both over-correction and under-treatment have the risk of leading to central pontine myelinolysis, manifesting as paralysis.
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Sodium food sources

The principal source of sodium in the diet is table salt (sodium chloride). Pickled and processed foods are good sources of sodium. It is also present in baking soda, monosodium glutamate (MSG), various seasonings, meat products, fish, poultry and dairy products. Plants and plant sources are generally poor sources of this nutrient. The minimum physiological requirement of sodium (Na) is 500 mg/day. The Adequate Intake for Na is 1.2 to 1.5 grams/day. The tolerable upper intake (UL) level for Na is 2.3 grams/day. Exceeding the UL could lead to hypertension and cardiac disease.

Sodium absorption and excretion

The absorption of sodium and water in the upper intestine depends on the presence of D-glucose. The active NA+ and glucose transport is by the Na+/glucose cotransporter (SGLT1). There is cotransport of water along with Na+ and sugar across the brush border membrane of enterocytes. The 3Na+/2K+ pumps on the basolateral membrane pump out Na+ towards the blood. The bulk of the sodium excreted is reabsorbed in the proximal tubule and ascending loop of Henle. A small quantity of sodium is delivered into the collecting duct for excretion in urine to maintain sodium balance.

Functions of sodium

Sodium is required for controlling blood pressure and blood volume. Another important function of Na+ is maintaining cellular osmotic processes. Na+ is required for transmitting nerve impulses and normal function of the nervous system. Optimum Na+ serum level is required for contraction of muscles.

Sodium deficiency disease causes

The primary causes of low Na+ serum levels are, loss of sodium from the body, loss of sodium and water from the body or increase in the volume of water in the system. Low Na+ serum levels are common in elderly. Several factors contribute to excess water or fluid in the body or depletion of Na+. Some of the causative factors are:
  • acute dietary deficiency,
  • excessive sweating,
  • polydipsia,
  • drinking too much water,
  • persistent vomiting,
  • severe diarrhoea,
  • fluid loss due to burns,
  • kidney failure,
  • congestive heart failure,
  • hepatic cirrhosis,
  • hypothyroidism,
  • adrenal insufficiency,
  • SIADH (syndrome of inappropriate anti-diuretic hormone),
  • inappropriate vasopressin secretion,
  • use of certain diuretics, antidepressants and anti-seizure medications,
  • use of psychoactive medicines like MDMA,
  • salt-wasting nephropathy,
  • cerebral salt wasting,
  • presence of tumors,
  • use of antineoplastic agents and
  • congenital chloride diarrhea.

Sodium deficiency signs and symptoms

When hyponatremia is sudden, acute and severe, cerebral edema occurs leading to brain damage. In chronic form of the disease, the following symptoms may be observed:
  • Weakness and tiredness,
  • muscle weakness,
  • lethargy,
  • restlessness,
  • loss of appetite,
  • nausea and vomiting,
  • headache,
  • giddiness,
  • increased falls,
  • gait abnormality,
  • altered posture and gait,
  • spasms or cramps,
  • irritability,
  • reduced attention,
  • confusion,
  • altered personality,
  • memory loss,
  • seizures,
  • fluid in the lungs,
  • respiratory arrest,
  • decreased consciousness and
  • coma.

Diagnosis of sodium deficiency

The symptoms of low Na+ serum levels varies among patients. Measuring the serum levels of Na+ is the best way of confirming the diagnosis. Medical history of the patient will help in arriving at the causative factor. Determining the type of hyponatremia (i.e. hypervolemic, euvolemic or hypovolemic) can help in taking treatment decisions.

Sodium deficiency diseases

As said earlier, the medical term for low Na+ serum levels is hyponatremia. Consumption of high volumes of fluid and excess loss of sodium are main precipitating factors. These fluid and sodium imbalances can be brought about by several factors listed above. Several systemic diseases can cause sodium deficiency in the serum.

Hyponatremia

Hyponatremia can set in suddenly and turn severe. In such acute state, water enters the brain cells causing cerebral edema. Herniation of the brain, brain stem compression and brain damage may occur. The acute deficiency state can also lead to fluid accumulation in the lungs and respiratory arrest. When the sodium serum level drop is gradual, the symptoms develop slowly over several days. Depending upon the causative factors, the type of hyponatremia (i.e. hypervolemic, euvolemic or hypovolemic) as well as the symptoms may vary.

Hyponatremia and tumors

Adedayo A. Onitilo et al. in their study "Tumor-Related Hyponatremia" concluded that,
"Hyponatremia occurs quite frequently in patients with tumors. The systemic manifestation of many types of tumors and the toxicities of cancer therapy are involved in the pathogenesis of hyponatremia of malignancies."
Pituitary tumors, craniopharyngiomas, lung, breast, head and neck tumors appear to cause inappropriate secretion of antidiuretic hormone, ectopic ADH secretion or inappropriate vasopressin secretion, leading to volume increase and cerebral salt wasting, resulting in serum deficiency of sodium. Antineoplastic agents such as vincristine, vinblastine and cyclophosphamide are known to cause high serum levels of vasopressin and inappropriate secretion of antidiuretic hormone, leading hyponatremia.

Hyponatremia and congenital chloride diarrhea

Congenital chloride diarrhea is due to mutations in the SLC26A3 gene resulting in intestinal SLC26A3 protein deficiency and impaired intestinal Cl(-)/HCO(3)(-) exchange. The mutation results in diarrhea-related sodium chloride and fluid depletion.

Sodium deficiency disease treatment

Mild drop in serum Na+ levels is treated by oral hydration and electrolyte replacement. In severe or acute cases, treatment often involves intravenous fluid and electrolytes restoration. The patient's blood volume status, also has to considered for selecting the treatment option. Further medications may be required to treat and manage the factors responsible for the sodium deficiency disease.
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References:
1.Wedenoja S, Ormälä T, Berg UB, Halling SF, Jalanko H, Karikoski R, Kere J, Holmberg C, Höglund P. The impact of sodium chloride and volume depletion in the chronic kidney disease of congenital chloride diarrhea. Kidney Int. 2008 Oct;74(8):1085-93.
2.Adedayo A. Onitilo, Ebenezer Kio, Suhail A. R. Doi. Tumor-Related Hyponatremia. Clin Med Res. 2007 Dec; 5(4): 228–237.
3.M Biswas, J S Davies. Hyponatraemia in clinical practice. Postgrad Med J. 2007 Jun; 83(980): 373–378.
4.Wakil A, Atkin SL. Serum sodium disorders: safe management. Clin Med. 2010 Feb;10(1):79-82.
5.Reynolds RM, Padfield PL, Seckl JR. Disorders of sodium balance. BMJ. 2006 Mar 25; 332(7543): 702–705.
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