ECF Osmoregulation

  • The osmolarity of the extracellular fluid (ECF) is ultimately determined by the total amount of solute (measured in milliosmoles) divided by the total volume of free water (measured in liters) within the ECF. Theoretically, ECF osmolarity could be manipulated by changing either variable. However, a critical concept is that extracellular fluid osmolarity is controlled purely by modulating the amount of free water within the ECF and not by changing the total amount of ECF solutes. In other words, the osmolarity of the extracellular fluid is regulated by diluting or concentrating the already-present solutes via adding or removing free water from the ECF. The addition and subtraction of free water is performed either by modulating the thirst instinct or controlling the osmolarity of the excreted urine.
ECF Osmole Composition
  • Empirically, the extracellular fluid typically displays an osmolarity of 300 mOsm/L with half being composed of positive ions and the other half being composed of negative ions. The vast majority of the positive ions are contributed by sodium with very minor contributions by potassium and even less so by magnesium and calcium. The significant majority of negative ions are contributed by chloride with a small contribution by bicarbonate and a very minor role played by negatively-charged proteins.
  • The ECF must ultimately possess an equal number of positive and negative ions to maintain its electroneutrality. Because the vast majority of positive ions are contributed by sodium, and it is assumed that a nearly equal quantitative number of negative ions will match those of sodium, the blood sodium concentration is clinically used as a proxy for the entire extracellular osmolarity. However, it should be emphasized that although sodium is used to measure extracellular osmolarity this does not mean that osmolarity is regulated by means of modulating ECF sodium amounts. Once again, and this cannot be emphasized enough, ECF osmoregulation is purely achieved by modulating the volume of extracellular fluid free water that dilutes the already present solutes and does not involve active modulation solutes.
  • Overview
    • Osmoregulation of the extracellular fluid is achieved by regulated addition and subtraction of free water from the extracellular fluid, thus diluting or concentrating the already present electrolytes. These processes are regulated by means of negative feedback control circuits which sense the extracellular fluid osmolarity and then coordinate free water addition and subtraction in an effort to maintain relatively stable values of osmolarity. When ECF osmolarity rises excessively, these mechanisms promote addition of free water to the ECF, thus reducing ECF osmolarity. In contrast, when ECF osmolarity drops excessively, these processes enhance water loss from the extracellular fluid, thus returning ECF osmolarity to its set point. Two basic mechanisms are at the body's disposal to modulate free water addition and subtraction: the behavioral drive for water intake (thirst) and control of the urine osmolarity.
  • Control of Thirst
    • Significant amounts of free water can be added to the ECF simply by ingestion, thus diluting the already-present electrolytes and in turn reducing the ECF osmolarity. The modulation of free water addition is achieved by control of the behavioral drive for free water, known as the thirst sensation. Although modulation of behavior may seem an unlikely method for regulating osmolarity, the drive for thirst is so powerful that it can maintain normal extracellular fluid osmolarity completely on its own even if other osmoregulatory mechanisms are dysfunctional, so long as the individual has access to free water.
    • The mechanism by which ECF osmolarity is linked to the thirst drive appears to depend on osmoreceptor-like cells located in the "Thirst Center" of the hypothalamus. These cells are stimulated by excessive increases in the extracellular fluid osmolarity and appear to modulate higher brain areas to coordinate the sensation of thirst and the behavioral seeking of water. Other physiological stimuli also appear to stimulate the thirst center; however, in most contexts extracellular fluid osmolarity appears to be the most important stimulus.
  • Control of Urine Osmolarity
    • The kidneys display a remarkable capacity to excrete urine with a wide range of osmolarity from a dilute urine of 50mOsm/L to one as concentrated as 1200mOsm/L, compared to the normal ECF osmolarity of 300mOsm/L. As will be discussed extensively in Regulation of Urine Osmolarity when the urine is more dilute than the ECF, this amounts to loss of free water from the ECF, thus concentrating the ECF. Conversely, when the urine is more concentrated than the ECF, this amounts to addition of free water to the ECF, thus diluting the ECF. The complex regulation and mechanisms underlying renal control of urine osmolarity are discussed further in regulation of urine osmolarity.