Sodium - Kresser Institute Membership Site

Marker Name: Sodium

REFERENCE RANGES FOR SERUM SODIUM:

Laboratory reference range: 134–144 nmol/L

Functional reference range: 135–140 nmol/L

DESCRIPTION:

Most of the body’s sodium (Na) is found in plasma, where it is the main extracellular cation. Sodium plays a key role in regulating extracellular fluid volume (ECF), blood pressure, osmotic equilibrium, and acid-base balance, and it contributes to the resting membrane potential across all cell membranes, which is important for muscle and nerve function.^1,2 Approximately 30 percent of sodium is found in nonexchangeable locations such as bone, but serum sodium concentration is a useful representation of total body sodium.³

Sodium cannot freely diffuse across cell membranes, but water can. When serum sodium concentration changes, water moves in and out of cells to maintain osmotic equilibrium between intracellular and extracellular fluid. Because of this phenomenon, abnormal serum sodium concentration primarily indicates a disorder of water balance (dehydration or overhydration), as opposed to a disorder of total plasma sodium. These changes in water balance do not cause a disorder in ECF volume (hypervolemia or hypovolemia) until the condition is extreme, because approximately two-thirds of water is intracellular and only one-third is extracellular.⁴

Serum sodium homeostasis involves the kidneys, intestines, and hypothalamus. It is primarily maintained by thirst and antidiuretic hormone (ADH, also referred to as vasopressin), which regulate water consumption and urinary water conservation, respectively.⁴

High serum sodium concentration (hypernatremia) is a disorder of too little water, or dehydration. It is most often caused by unreplaced loss of fluid that is hypotonic to plasma; that is, loss of fluid that has a concentration of osmotically active electrolytes (i.e., sodium plus potassium) that is lower than the concentration of sodium in plasma. Hypernatremia can also be caused by sodium overload or excessive glycogen breakdown. A complete list of specific conditions that can cause high serum sodium is provided below. Water intake corrects hypernatremia, so prolonged hypernatremia requires either impaired thirst, which is most often caused by hypothalamic lesions or mental illness, or lack of independent access to water, which most often occurs with infants and the elderly.³

Low serum sodium concentration (hyponatremia) is a disorder of too much water, or overhydration. It can be caused by advanced renal failure, malnourishment, primary polydipsia (increased thirst), reduced effective arterial blood volume, syndrome of inappropriate ADH secretion (SIADH), certain endocrine disorders (adrenal insufficiency, hypothyroidism), pregnancy, extreme exercise, hyperglycemia, absorption of irrigant solutions during surgery, and many drugs. Pseudohyponatremia can occur when the plasma water fraction is decreased by abnormally high serum protein or fat content. Hyponatremia is unusual if the ability to dilute urine is intact, because the maximum attainable urine volume in normal circumstances is over 10 L/day, while normal water intake is under 2.5 L/day. A complete list of disorders that can cause hyponatremia is provided below.

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:³

Dehydration due to unreplaced loss of fluid that is hypotonic to plasma. Effect is transient, unless thirst or water access is inhibited.
- Water losses (insensible, sweat)
- Gastrointestinal water losses (vomiting, osmotic diarrheas)
- Urinary water losses
  - Central or nephrogenic diabetes insipidus
  - Osmotic diuresis, due to:
    - High glucose (as seen in uncontrolled diabetes mellitus)
    - Urea (as seen in high-protein tube feedings)
    - Mannitol therapy
  - Hypothalamic lesions impairing thirst or osmoreceptor function
    - Adipsic diabetes insipidus
    - Primary hypodipsia
    - Primary mineralocorticoid excess
  - Sodium overload (effect is transient, unless thirst or water access is inhibited)
    - Intake or administration of hypertonic sodium solutions
    - Sodium poisoning
  - Water loss into cells due to glycogen breakdown (effect is transient)
    - Extreme exercise
    - Seizures
  - Drugs
    - Loop diuretics⁴

Low in:⁵

Low dietary solute intake
- Beer drinker’s potomania
- Malnourishment
Primary polydipsia, due to:
- Some psychiatric illnesses
- Hypothalamic lesions affecting thirst center (as seen in sarcoidosis)
Advanced renal failure
Elevated ADH (antidiuretic hormone)
- Hormonal changes
  - Adrenal insufficiency
  - Hypothyroidism
  - Pregnancy
- Extreme exercise (e.g., marathon, ultra-marathon, desert hikes)
- Reduced effective arterial blood volume
  - True volume depletion (vomiting, diarrhea)
  - Decreased tissue perfusion (heart failure, cirrhosis)
- Syndrome of inappropriate ADH secretion (SIADH), due to:⁶
  - Any central nervous system disorder (e.g., stroke, hemorrhage, infection, trauma)
  - Ectopic production of ADH by a tumor (e.g., small cell carcinoma, olfactory neuroblastoma, head and neck cancer)
  - Surgical procedures
  - Pulmonary diseases (e.g., pneumonia, asthma, atelectasis, acute respiratory failure, pneumothorax)
  - Hormone deficiency (e.g., hypopituitarism)
  - Exogenous hormone treatment (e.g., vasopressin, desmopressin, oxytocin)
  - Symptomatic HIV infection
  - Certain genetic disorders
    - Nephrogenic syndrome of inappropriate antidiuresis
    - Polymorphisms in genes encoding the hypothalamic osmoreceptor
  - Movement of water out of cells
    - Hyperglycemia
    - Mannitol therapy
  - Absorption of irrigant solutions (glycine, sorbitol, mannitol) during surgery
  - Pseudohyponatremia, due to decreased plasma water fraction (laboratory artifact)
    - Hyperlipidemia
    - Cholestatic and obstructive jaundice (lipoprotein X)
    - Multiple myeloma
  - Drugs
    - Thiazide diuretics
    - Nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, naproxen)
    - Ecstasy or MDMA intoxication
    - Opiates (e.g., codeine, morphine)
    - Ciprofloxacin
    - Selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline)
    - Tricyclic antidepressants (amitriptyline)
    - Monoamine oxidase inhibitor antidepressants
    - Certain antipsychotics (e.g., carbamazepine, oxcarbazepine, thiothixene, thioridazine, haloperidol)
    - Antiarrhythmic agents (lorcainide, amiodarone)
    - Chemotherapy drugs (high-dose intravenous cyclophosphamide, vincristine, vinblastine, vinorelbine, cisplatin, melphalan, ifosfamide, methotrexate, high-dose imatinib)
    - Chlorpropamide
    - Interferon-alpha
    - Interferon-gamma
    - Sodium valproate
    - Bromocriptine

FUNCTIONAL RANGE INDICATIONS:

High in:

Functional dysglycemia (check other markers of glycemic dysregulation)
HPA axis dysregulation (more likely hyperfunction)
Cushing’s disease
Mild dehydration

Low in:

Functional dysglycemia
Hypothyroidism
HPA axis dysregulation (more likely hypofunction)
Addison’s disease or glucocorticoid-induced adrenal insufficiency

References: