Question 23

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. 

Discussion

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)

Skøtt, Ole. "Body sodium and volume homeostasis." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 285.1 (2003): R14-R18.

Heer, Martina. "Sodium regulation in the human body." Current Sports Medicine Reports 7.4 (2008): S3-S6.

Bie, Peter. "Mechanisms of sodium balance: total body sodium, surrogate variables, and renal sodium excretion." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 315.5 (2018): R945-R962.

Edelman, I. S., and J. Leibman. "Anatomy of body water and electrolytes." The American journal of medicine 27.2 (1959): 256-277.

Widdowson, Elsie M., E. A. McCance, and Christine M. Spray. "The chemical composition of the human body." Clinical Science 10 (1951): 113-125.

ICRP. Reference man: anatomical, physiological and metabolic characteristics. 1975.

Forbes, R. M, A. R. Cooper, and H. H. Mitchell. "The composition of the adult human body as determined by chemical analysis." Journal of Biological Chemistry 203 (1953): 359-366.

Forbes, R. M., H. H. Mitchell, and A. R. Cooper. "Further studies on the gross composition and mineral elements of the adult human body." Journal of Biological Chemistry 223 (1956): 969-975.

Kiela, Pawel R., and Fayez K. Ghishan. "Physiology of intestinal absorption and secretion." Best practice & research Clinical gastroenterology 30.2 (2016): 145-159.

Sandle, G. I. "Salt and water absorption in the human colon: a modern appraisal." Gut 43.2 (1998): 294-299.

Michell, A. R. The clinical biology of sodium: the physiology and pathophysiology of sodium in mammals. Elsevier, 2014.

Spiller, R. C. "Intestinal absorptive function." Gut 35.1 Suppl (1994): S5-S9.

Fordtran, John S., Floyd C. Rector, and Norman W. Carter. "The mechanisms of sodium absorption in the human small intestine." The Journal of clinical investigation 47.4 (1968): 884-900.

Brody, T. "Inorganic nutrients." Nutrition biochemistry (1999): 761-794.

Heer, Martina, et al. "High dietary sodium chloride consumption may not induce body fluid retention in humans." American Journal of Physiology-Renal Physiology 278.4 (2000): F585-F595.

Davis, Daniel P., et al. "Exercise-associated hyponatremia in marathon runners: a two-year experience." The Journal of emergency medicine 21.1 (2001): 47-57.

Titze, Jens, et al. "Osmotically inactive skin Na+ storage in rats." American Journal of Physiology-Renal Physiology 285.6 (2003): F1108-F1117.

Selvarajah, Viknesh, et al. "Novel mechanism for buffering dietary salt in humans: effects of salt loading on skin sodium, vascular endothelial growth factor C, and blood pressure." Hypertension 70.5 (2017): 930-937.

Selvarajah, Viknesh, et al. "Skin sodium and hypertension: a paradigm shift?." Current hypertension reports 20.11 (2018): 1-8.