Permeability coefficients have been measured in single microvessels mainly in mesentery but also in other tissues including skeletal muscle, brain, lung, and kidney. Estimates of microvascular permeability have also been made for capillary beds in different organs and tissues. Because many millions of capillaries may contribute to net transport here, values are obtained for the products PJS and LPS. The value of S, the area of microvascular wall, may be estimated from the histology of the tissue assuming that the number of perfused vessels per unit volume is same in the tissue prepared for histology and in that where the permeability measurements were made. (For methods of permeability measurement, see article in this volume on "Regulation of Vascular Permeability" by D. O. Bates.)
There is reasonably good agreement between estimates of Pd and LP obtained from whole tissues and organs and for single vessels in the same tissue. There is, however, great variation between the mean values of LP and Pd to the smaller hydrophilic solutes in different microvascular beds. In vessels with fenestrated endothelium, LP and Pd for low-molecular-weight water-soluble solutes vary directly with the number of fenestrations per unit area of endothelium. Values for the Lp of fenestrated vessels are different in different tissues. Thus in the fenestrated ascending vasa recta in the renal medulla, Lp may exceed 10-5cmsec-1cm H2O-1, whereas in fenestrated vessels of the intestinal mucosa, Lp is in the range of 10-6cmsec-1cm H2O-1, reflecting the lower density of the endothelial fenestrations on the intestinal capillaries. The LP of vessels with continuous nonfenestrated endothelium varies between 10-6 and 10-9cmsec-1cm H2O-1, depending on the tissue of origin, and similar variations are seen in Pd. Here, the ultrastructural basis of variable permeability is less obvious. Although electron micrographs of muscle capillaries and mesenteric capillaries look similar, both types of vessel appearing as tubes of flattened endothelial cells lacking fenestrations and joined by junctions of similar ultrastructure, LP values for mesenteric capillaries are 20 to 50 times greater than LP for muscle microvessels. Similar differences are seen for values of Pd to NaCl in mesenteric and muscle microvessels (see Figure 1A). The differences in permeability reflect different frequencies of breaks in the strands of tight junctions that join adjacent cells. At present, detailed ultrastructure of the intercellular junctions is known only for heart muscle and mesenteric capillaries. The sieving properties of these two types of vessel, however, are very similar and in both vessel types, Pd falls rapidly as solute molecular radius approaches 40 A.
Although microvascular LP and Pd for small water-soluble molecules vary greatly from one tissue to another, LP bears a constant relation to Pd for a given solute (e.g., inulin). Figure 1B shows that variations in Pd to NaCl and inulin in different tissues are directly proportional to varia tions in LP. This is strong evidence that the permeability pathways for small hydrophilic solutes are principally those used for fluid exchange.
By contrast, s to macromolecules is very similar in all normal microvessels. The value for serum albumin is between 0.85 and 0.99 in nearly all microvascular beds (see Figure 1D). Such values are essential for normal fluid balance (see later discussion). This is indicative of a common structure in all microvascular walls that is responsible for molecular sieving. At present, the favored candidate for this structure is the luminal glycocalyx of the endothelial cells, and this hypothesis has been boosted by several recent reports.
A fall in s and a rise in LP is characteristic of the increase in permeability seen in acute inflammation.
While s for macromolecules approaches unity as molecular radius approaches 40 to 50 A, finite permeabilities have been measured for all naturally occurring macromolecules. These lie in the range of 10-9 to 10-8cmsec-1. Whereas smaller hydrophilic molecules pass through channels in microvascular walls that have a limiting size of 40 to 50 A (molecular radius), macromolecular permeability involves different pathways. There is evidence for two mechanisms: transcytosis by endothelial caveolae that act as shuttles across the cell; or convection through a minute number of large pores (radius ~250 A) consisting of transcellular channels formed by fusion of caveolae or by occasional open intercellular junctions.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.