We propose to study blood-lymph transport of plasma proteins and other large molecules in normal animals and in animals with experimental disturbances of fluid and protein distribution, and also to study blood-tissue exchange of these substances in whole animals and in isolated perfused organs. Our goals are to find out how large molecules, especially albumin and immunoglobulins, move through the capillary endothelium and how they become distributed throughout the interstitial compartment. We are particularly interested in how macromolecular transport is coupled to fluid movement, how fluid balance between plasma and interstitium is controlled under normal and abnormal conditions, and how abnormalities of fluid and plasma protein exchange affect delivery of albumin and immunoglobulins to the tissues. Abnormal states to be investigated include acute and chronic hypoproteinemia, volume expansion with plasma or colloid substitute or saline fluid, venous congestion and chronic mild inflammation. We will explore the influence of molecular size, shape and charge on transport parameters (permeability-surface area products and reflection coefficients), and be on the lookout for specific transport affinities for individual plasma proteins. An important part of our plan is to advance theoretical analysis of blood-tissue-lymph exchange in order to evaluate capillary transport pathwasy and interstitial barriers. Our investigations will further understanding of plasma and interstitial fluid volume control under normal conditions, and of how these control mechanisms are affected in edematous states (congestive heart failure, hypoproteinemia) or when plasma volume is restored with artificial colloid or saline fluids after blood loss. We hope to learn more about the ways in which the body resists development of edema, and how we may intervene more successfully to restore normal fluid and protein distribution.
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