Regulation of extracellular volume

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Approximately 50-70% of total adult body weight is water. In the male, 20% of the total body weight is accounted for by extracellular fluid (consisting of 15% extravascular volume and 5% plasma) while 40% of the total body weight is accounted for by intracellular fluid (4% red blood cells). In the female, 15% of the total body weight is accounted for by extracellular fluid (11% extravascular volume and 4% plasma), while 35% is accounted for by intracellular fluid (3% red blood cells).

Anions, such as chlorine and bicarbonate are predominantly found extracellularly, in plasma and interstitial fluid. In terms of cations, potassium is predominantly found intravascularly (~140mMol/L), while sodium is predominantly found extravascularly (~140mMol/L). Sodium therefore is essential in determining the volume of extracellular fluid, since it will force an equilibrium. A steady state sodium balance is maintained by excreting and ingesting approximately 170 mmol of sodium daily. Normally, sodium excretion is through the kidneys and is regulated.

If there were a net gain of sodium chloride in the body, it would aggregate extracellularly, resulting in the dehydration of cells, and increased extracellular fluid volume due to osmosis. Conversely, if there were a net loss of sodium chloride, it would result in a hypotonic solution, perhaps bursting cells with too much water. In terms of how they would affect the osmotic composition and production of urine, I simply don't know.

A positive sodium balance, however, stimulates antidiuretic hormone (ADH) release by increasing plasma volume, thereby also increasing venous pressure, venous return and right atrial pressure. ADH will then increase intracellular cyclic AMP concentrations, which in turn causes increased water reabsorption. This, coupled with a concurrent increase in membrane permeability to water, staves off dehydration.

Altering extracellular volume

Extracellular volume can be altered by creating conditions in which cells are hypotonic, hypertonic, or isotonic. So, if pure water is infused into the blood, the net result would be a hypotonic extracellular solution in which cells would absorb water and expand. Since normal saline is isotonic, its infusion would have no net osmolar effect, but would simply increase plasma volume without altering tonicity. I don't know what the hell half-normal saline is, but since we haven't yet tackled hypertonicity, let's say that it's that and that the extracellular volume would soak out water, thereby dehydrating cells.

Objectives

  • Given the body weight, estimate:
    1. total body water
    2. extracellular water
    3. intracellular water
    4. blood volume
    5. plasma volume
  • Identify normal extracellular fluid osmolality and concentrations of Na+, K+, Cl-, HCO3- and proteins, and contrast these values with those for intracellular fluids.
  • Define the role of Na+ in determining the volume of extracellular fluid.
  • Predict the changes in extracellular and intracellular volumes and osmolarities caused by infusion of 1 L water, 1 L normal saline, and 2 L of half-normal saline.
  • Identify the normal level of Na+ ingestion and major routes of Na+ loss from the body.
  • Predict the changes in body fluid volume and osmolality caused by a net NaCl loss or gain in the body. Predict how each of these disturbances would alter the rate of urine production and the osmotic composition of the urine.
  • Describe the the neural reflex regulation of renal Na+ and water excretion.
  • Describe the regulation of Na+ reabsorption along the nephron, including the effects of sympathetic nerves, angiotensin II, aldosterone and antidiuretic hormone (ADH, vasopressin).
  • Identify major routes and normal ranges for water intake and loss, and predict how changes in intake and loss affect the distribution of total body water.
  • Identify the most powerful stimuli that cause ADH release, and describe the negative feedback control mechanisms for each.
  • Predict the changes in body fluid volume and osmolality caused by a net water loss or gain in the body. Predict how each of these disturbances would alter the rate of urine production and the osmotic composition of the urine.
  • Describe the molecular mechanism by which ADH increases renal tubule permeability to water. Identify causes of diabetes insipidus.