The body fluids found outside the cells, such as plasma (the liquid portion of blood and lymph), and interstitial fluid, are generically termed extracellular fluid. Three-fourths of all extracellular fluid is stored as interstitial (between cells) fluid, and one-fourth as plasma. Cells in the tissues are separated from one another by spaces called interstitium, usually filled with a fibrous complex termed extracellular matrix. This structure is formed by collagen and elastin fibers and elongated glycoproteins, also containing proteoglycan filaments that form a hydrophilic gel. Whereas collagen and elastin fibers have a structural function, proteoglycan form a network of coiled thin filaments, mainly constituted by hyaluronic acid, which entrap a viscous fluid known as interstitial fluid, rich in nutrients, ions, hormones, and other molecules necessary to cellular function. The interstitial fluid has almost the same composition of plasma, except for having much lower protein concentrations, and it is filtered to the extracellular matrix from the capillary vessels by diffusion (i.e., capillary pressure).
However, the plasma proteins also exert osmotic pressure (plasma colloid osmotic pressure), leading fluid from the interstitium back to capillaries, thereby avoiding a significant loss of water in the blood.
The extracellular fluid filtered from the blood vessels (arterial capillaries) into the extracellular matrix flows among the cells transporting nutrients and chemical messengers and receives from cells metabolites, ions, proteins, and other substances, and is then reabsorbed by either the venous or the lymphatic capillaries. Substances with a low molecular weight present in the interstitial fluid are easily absorbed through the venous capillary walls into the blood, whereas those with high molecular weight such as proteins are absorbed by the lymphatic capillaries. The circulating lymph is, therefore, originated from the extracellular fluid. The ionic compositions of plasma and interstitial fluid are also similar, due to the high permeability of capillary membranes that separate these two media.
The regulation of extracellular fluid volume is crucial to avoid edema and for the maintenance of arterial pressure. Edema, or the excessive accumulation of fluid in tissues, is normally prevented by the elimination of water and specific amounts of ions through diuresis, perspiration, and feces, along with other regulatory mechanisms that avoid excessive loss of water from the organism as well. There are three safety mechanisms that prevent serious edema: 1), elimination of interstitial fluid protein concentrations, which reduces colloid osmotic pressure and increases capillary filtration; 2), increased lymphatic flow; and 3), the interstitial gel formation that prevents the easy flow of fluid through the tissues at the negative pressure range of less than one atmosphere (about 3mm Hg). However, hormonal or electrolytic imbalance, deregulation of renal functions, heart failure, and other factors affecting protein plasma levels or capillary permeability, as well as certain diseases and/or trauma, can cause the accumulation of an excess of extracellular fluid in tissues. Depending on the affected system and the degree of extracellular edema, serious physiological impairing conditions, even shock and death may occur.
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