Cellular aspects of transvascular exchange: a 40-year perspective.

Study of the microcirculation began with microscopic anatomy in the 17th century, but it was not until the mid-19th century that the concept of microcirculatory exchange was developed, in association with the great expansion in knowledge of physical chemistry and cell biology. In the first half of the 20th century, the roles of diffusion and osmosis (ultrafiltration) were put on a quantitative foundation and the physiological basis for regulation of the microcirculation was established. During the past 40 years, our understanding of transvascular exchange has been deepened and widened through two major developments: 1) the application of electron microscopy to the study of microvascular structure and 2) the use of sophisticated physical and mathematical models of passive transport processes to analyze and interpret experimental data. In the past few years, the focus of microvascular research has been returning to cell biology and the role of endothelial cells in controlling transvascular exchange. The 21st century holds promise of many exciting new developments.