SODIUM

sodium ion

• Sodium balance is directly related to water balance (water goes to where sodium goes).
• Both sodium and water are either reabsorbed or excreted in the renal tubules-- which are regulated by a variety of factors listed below.
• Because the levels of sodium and water in the blood are related to their levels in the urine, the diagnosis of hypo- and hyper-natremia must take into account serum sodium, serum osmolality, urine sodium, and urine osmolality.
• In general, serum and urine osmolality reflect water balance thus suggest ADH activity level; whereas, serum and urine sodium levels reflect renal salt excretion activity thus suggest renal function and RAAS activity level.

sodium, water regulation, ADH
SODIUM REGULATION (left): Sodium ions are excreted to the urine from blood in response to too much sodium or water (effective circulating fluid or ECF) in the blood. Diuretics and natriuretic peptides act on renal tubular channels to increase sodium (hence water) excretion. On the other hand, sodium ions are resorbed back to the blood in response to low sodium or water (ECF) level. Angiotension II and aldosterone act on renal tubular channels to increase sodium (hence water) resorption.

WATER REGULATION (right): Water ions are normally resorbed from urine into the blood via aquaporins V2 receptors under the action of ADH. This excreted to the urine from blood in response to too much sodium or water (effective circulating fluid or ECF) in the blood. Diuretics and natriuretic peptides act on renal tubular channels to increase sodium (hence water) excretion. On the other hand, sodium ions are resorbed back to the blood in response to low sodium or water (ECF) level. Angiotension II and aldosterone act on renal tubular channels to increase sodium (hence water) resorption.

hyponatremia - hypernatremia


HYPONATREMIA
normonatremia
HYPERNATREMIA

HYPONATREMIA

ISOTONIC (pseudohyponatremia) The presence on non-aqueous solute (lipids, proteins) raises the total body of plasma thus lowering the Na concentration per volume of plasma. However, it does not raise the serum tonicity or osmolality.

  ✧ hyperlipidemiaSeen in hypertriglyceridemia (often associated with pancreatitis, DKA), hypercholesterolemia (associated with cholestatis)

  ✧ hyperproteinemiaSeen in mono and polyclonal gammopathy such as multiple myeloma, amyloidosis, etc,.. More examples here.


HYPERTONIC The presence on aqueous solute (glucose, mannitol, maltose, sucrose) raises the serum tonicity or osmolality thereby drawing water out of cells and lowering serum Na concentration.

  ✧ hyperglycemiaSeen in DKA and HHS

  ✧ mannitol infusionUsed in treatment of traumatic brain injury

  ✧ ivig infusionOften prepared in mannitol, maltose or sucrose solution


HYPOTONIC
✿ Extra-renal salt loss Low Na intake decreases serum osmolality which inhibits water reabsorption across the renal tubules leading to low urine osmolality (< 100) and low urine Na (< 20)

  ✧ low salt dietSuch as 'tea and toast' diet


✿ Extra-renal h2o gain High water or hypotonic fluid intake increases blood volume (effective circulating fluid or ECF) which inhibits water reabsorption across the renal tubules leading to low urine osmolality (< 100) and low urine Na (< 20)

  ✧ beer potomaniaDrinking large amount of beer containing very low solute

  ✧ primary polydypsiaIncreased water intake due to psychiatric illness or increased thirst (hypothalamic disease)


✿ Renal salt loss/ h2o gain
  ✧ advanced renal diseaseIn advanced CKD or severe AKI, poor Na resabsorption capability (high urine Na, > 20) lowers serum osmolality thereby inhibiting H2O reabsorption leading to high urine osmolality (200-250)

  ✧ adrenal insufficiencyLow aldosterone leads to decreased Na absorption (high urine Na) and volume depletion, which stimulates ADH release and increased water absorption. Low cortisol leads to low cardiac output and low ECV, it also stimulates release of CRH, which in turn stimulates release of ADH.

  ✧ diureticsInclude thiazide and, though less often, loop diuretics. Thiazide inhibits Na reabsorption in distal tubule and increases water permeability and reabsorption at the collecting duct leading to hyponatremia. Loop diuretics inhibits Na reabsorption at the loop of Henle reducing the osmotic gradient in the medullary interstitium resulting in decreased water reabsorption and the net effect might or might not be hyponatremia.

  ✧ siadh In syndrome of inappropriate ADH secretion (SIADH), ADH stimulates water reabsorption across the renal tubules leading to concentrated urine (high urine osmolality, > 300), high urine Na (> 40), low serum osmolality, and hyponatremia. Serum Uric Acid and BUN are often low (< 4 and 5, respectively) due to increased uric acid renal clearance. More on etiologies of SIADH here.

  ✧ reset osmostatADH release is suppressed at an abnormally low osmolality (hyponatremic level where patients chronically live). Thus at normal osmolality level, ADH activity will not be suppressed leading to hyponatremia. Seen in chronic illnesses, pregnancy.

  ✧ cerebral salt wastingOften seen in subarrachnoid hemorrhage, meningitis, encephalitis, CNS malignancy, post neurosurgery. Caused by either the removal of central stimulation or inhibition by BNP on renal tubular Na channels leading to decreased Na reabsorption and high urine Na (> 20)

  ✧ low effective circulating volume (ecv) Low ECV stimulates both water and Na reabsorption via renal tubules causing high urine osmolality and low urine Na (< 20). In addition, ADH release is stimulated leading to a net effect of hyponatremia. Low ECV is seen in hypovolemia (dehydration, GI losses, hemorrhage), heart failure, cirrhosis, or low oncotic pressure (nephrotic syndrome, hypoalbuminemia).

    ☼ hypovolemiaCaused by ehydration, GI losses (diarrhea, vomiting), hemorrhage, heart failure, cirrhosis, or low oncotic pressure (nephrotic syndrome, hypoalbuminemia).

    ☼ heart failureCaused by ehydration, GI losses (diarrhea, vomiting), or hemorrhage

    ☼ cirrhosisSystemic vasodilation leads to leaky vessels thereby decreasing blood volume which then triggers ADH release thereby impairing water excretion and further decrease blood volume

    ☼ nephrotic syndromeLow serume protein level leads to low oncotic pressure to keep water intravascularly

    ☼ systemic vasodilationSeen in high inflammatory state such as acute pancreatitis, post op state, sepsis

HYPERNATREMIA

✿ Extra-renal salt gain High serum osmolality stimulates water reabsorption resulting in increased urine osmolality. High serum Na level inhibits Na reabsorption from the urine leading to high urine Na level. The net effect is net salt gain with high serum Na level and serum osmolality.

  ✧ excessive salt ingestionAccidental or surreptitious ingestion

  ✧ hypertonic saline infusionUsed in treatment of traumatic brain injury and hyponatremia

  ✧ sodium bicarb infusionUsed in treatment of metabolic acidosis

  ✧ isotonic saline replacementUsed to replace hypotonic fluid loss from osmotic diuresis (diabetes, recovery from azotemia), nasogastic suction, or loop diuretic therapy


✿ Extra-renal h2o loss Loss of fluid causes low blood volume (and increased serum osmolality) hence lowers effective circulating fluid (ECF). This stimulates more water and salt reabsorption from renal tubules resulting in increased urine osmolality and decreased urine Na level.

  ✧ skin lossSignificant sweat (and water) loss during exercise or sensible loss during fever, hot weather

  ✧ gi lossIncludes vomiting, GI drainage, and osmotic (not secretory) diarrhea

  ✧ low water intakeLack of access to water, altered mental status

  ✧ hypodipsia Impaired thirst caused by hypothalamic lesions (metastatic cancer, craniopharyngioma, stroke, trauma, SAH, TB, sarcoidosis)


✿ Renal h2o loss
  ✧ diabetes insipidus In central and nephrogenic DIs (causing reduced ADH production and ADH resistance, respectively), water is not reabsorpted from the tubular lumen leading to diluted urine (low urine osmolality) and polyuria. Concentrated blood (high serum osmolality) and hypernatremia often cause increased thirst. More on etiologies of DIs here.

  ✧ osmotic diuresis Large amount of glucose (in diabetes), mannitol, urea (during recovery period after azotemia or post obstruction) in the urine increase urine osmolality which draws more water into the tubules and effectively raising serum Na level and osmolality.

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