Capillary Permeability to Plasma Proteins.

ACCORDING to the classical hypothesis of Starling (1896) the exchange of water and small lipid-insoluble molecules across the capillary membrane is largely governed by the balance between hydrostatic and colloid osmotic pressures, the existence of the latter being dependent upon relative impermeability of the capillary membrane to plasma proteins. Starling's concept has been verified by direct experimental measurements (Landis, 1927; Pappenheimer and Soto-Rivera, 1948) and its essential features are no longer in dispute. In recent years, however, attention has been drawn to the fact that considerable quantities of plasma proteins pass through the capillary walls. Drinker and Field 1(1931) collected lymph from the cervical, leg and renal lymphatics, as well as from the thoracic duct, and found considerable concentrations of protein in all samples; they concluded that "the capillaries practically universally leak protein" and that this protein can only return to the blood stream via the lymphatic system. This concept of a continuous exchange of plasma proteins between plasma and extravascular compartments has been confirmed repeatedly with radioactively labelled plasma proteins (e.g., Wasserman and Mayerson, 1951; Yoffey and Courtice, 1956). 13I-labelled albumin turnover studies in the human subject indicate an overall exchange rate between intraand extravascular pools of 117-234% (mean 140%) of the total plasma albumin per day; and the total amount of albumin in the extravascular pool is greater than that in plasma (Cohen, Freeman and McFarlane, 1961). Leakage of plasma proteins may be of importance in that it enables antibodies to reach the tissues, and certain hormones such as insulin to exert their direct effect on the tissues (Hechter and Lester, 1960). Other hormones (e.g., thyroxine and cortisol) are partly bound by plasma proteins, and many drugs are known to be bound by plasma albumin. There is also evidence that the presence of plasma proteins in the interstitial fluid plays a part in the maintenance of normal tissue electrolyte content (Carey and Conway, 1954; Creese and Northover, 1961) and that the large extravascular reserve of plasma protein is drawn upon when protein is rapidly removed from the blood stream (Wasserman, Joseph and Mayerson, 1956; Cope and Litwin, 1962). In this article the mechanism of protein leakage through capillary walls, the methods available for measuring the leakage, and the factors that control it will be reviewed.