Question 23

Describe the regulation of sodium in the body. 

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College Answer

This question was generally poorly answered. Total body sodium is regulated within 2% in normal individuals. The vast majority is contained in the extracellular compartment. While any physiological regulation involves a balance of input and output, sodium intake is essentially unregulated in humans. Output is regulated via renal, gastrointestinal and skin losses. Candidates needed to present the renal handling of Na including hormonal control and present factual knowledge about the level of absorption and GFR effects to attain a pass mark. Many candidates focused on osmolality and tonicity and some on the use of diuretics thereby not gaining marks 
on regulation of sodium. Most candidates didn’t mention either the skin and GIT role in sodium  balance. 


Distribution of sodium

  • Total: 60mmol/kg: 30% non-exchangeable (locked up in bone and soft tissue)
  • 70% exchangeable
    • 15% exchangeable bone store
    • 10% in connective tissue muscle and skin (exchangeable buffer for dietary sodium)
    • 45% dissolved in body water
  • Of the dissolved sodium:
    • 30% in interstitial fluid
    • 10% plasma 
    • 2.5% transcellular fluid
    • 2.5% intracellular fluid

Regulation of sodium intake

  • Daily dietary intake of ~50-100mmol/day 
  • Aldosterone regulates colonic absorption to some minor extent
  • Glucose-coupled and Na+/H+ exchange accounts for most of the intestinal absorption
  • Total stool content 30 mmol/L, = only 3mmol/day is excreted in this way (i.e. almost 100% of dietary sodium is absorbed)

Regulation of intracellular/extracellular balance

  • Cellular membranes have very poor sodium permeability
  • Na+/K+ ATPase maintains high extracellular (135-145 mmol/L) and low intracellular concentration (10-15 mmol/L)

Sodium sequestration in skin and connective tissue

  • Bound to negatively charged residues on glycosaminoglycans
  • Not osmotically active
  • Serves as a buffer to prevent haemodynamic changes from dietary sodium fluctuations

Regulation of sodium and water elimination

  • This is the main mechanism of adjusting extracellular sodium concentration
  • The regulatory mechanisms mainly adjust sodium and water content of the urine by acting on the water and sodium reabsorption in the distal nephron
    • by adjusting glomerular filtration 
    • by increasing or decreasing the reabsorption of water (by vasopressin)
    • by increasing or decreasing the reabsorption of sodium (by aldosterone) 
  • Angiotensin II (increases reabsorption by increasing Na+/K+ ATPase activity in the proximal tubule, and increases NHE3 activity)
  • Aldosterone (increases ENaC activation in the collecting duct and Na+/K+ ATPase activity in the thick ascending limb)
  • Vasopressin (increases expression of ENaC in the collecting duct and NKCC2 in the thick ascending limb)
  • Catecholamines by increasing NKCC2 expression in the thick ascending limb

Unregulated sources of sodium loss in the ICU

  • Sweat  (in the unacclimatised, sweat contains up to 60mmol/L of sodium)
  • NG drainage (erratic, 10-120 mmol/L)
  • Ileostomy output (~120 mmol/L)
  • Wound drain, pleural drain, burns (same as normal ECF, 135-145 mmol/L)


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