Most clinical laboratory tests utilize interstitial and extravascular such as blood, urine, cerebral spinal fluid (CSF), and saliva. For example, CSF is monitored in the context of cancer for both diagnostic and therapeutic reasons. And yet, our understanding of the makeup of interstitial fluids, their relationships to disease, as well as their commercial importance in therapeutics and diagnostics remains rudimentary. Although sometimes perceived as static, interstitial and extravascular fluids are surprisingly dynamic. More than half of serum albumin is in the extravascular space. These fluids move rapidly between the intravascular and extravascular spaces - one entire plasma volume is exchanged very nine hours. In the first half of the book, the authors cover fundamental concepts of interstitial fluids, including their composition and function. They then further review the mechanisms by which interstitial fluids are regulated, characterizing the importance of hyaluronan - a major constituent of interstitial spaces and an a component of synovial fluid; and, outlining the regulation of proteolysis in the interstitial space.
In the second half of the book, the authors focus on the coagulation system. This system has been studied extensively in the context of vascular spaces. But many of its components exist in the interstitial spaces. Chapters are devoted to the fibrinolytic system, kallikrein, matrix metalloproteinases, coagulation factors, and protease inhibitors - all are interstitial. By covering a unique array of topics with broad application to biomedical scientists, this book expands our understanding of the importance of interstitial spaces and the fluids that move through and reside in this extravascular environment.
Composition and Function of the Interstitial Fluid Definition of Interstitial Fluid Extravasation Cell Secretion in Interstitial Space Connectivity of the Interstitial Fluid and Other Extravascular Fluids Relationship of Interstitial Fluid to Lymph Structure of the Interstitium Heterogeneity in the Interstitium Methods for Obtaining Interstitial Fluid and Some Diagnostic Applications Transport of Drugs and Biologicals in Interstitial Fluid Transport of Drugs in the Interstitial Space. Transport of Biologicals in the Interstitial Space. Tumor Interstitial Fluid Chapter 2 - The Extracellular Matrix, Basement Membrane and Glycocalyx Matrices which Modulate Interstitial Fluid Composition The Extracellular Matrix Basement Membrane Glycocalyx Chapter 3 - The Biochemistry of Hyaluronan in the Interstitial Space Hyaluronan Introduction to Hyaluronan Physical Characteristics of Hyaluronan The Effect of Protein on Hyaluronan Conformation Solvent and Hyaluronan Hyaluronan in the Interstitial Space Effect of Hyaluronan on Enzyme Activity Specific Interaction of Hyaluronan with Receptors (Hyaldherins) CD44 RHAMM Other Cell Surface Receptors for Hyaluronan Hyaluronan Binding to Other Hyaldherins Low Molecular Weight Hyaluronan Hyaluronan as a Therapeutic Hyaluronidase and Drug Delivery in the Interstitial Space Proteolysis in the Interstitium Proteolytic Enzymes in the Interstitial Space ADAM Proteases ADAMTS Proteases Comment on Proteolytic Enzymes in the Interstitial Space The Fibrinolytic System in the Interstitial Space Components of the fibrinolytic system The Fibrinolytic System in the Interstitial Space Origin of Components of the Fibrinolytic System Found in the Interstitium Effect of Hyaluronan on Components of Fibrinolytic System. Urokinase-Type Plasminogen Activator Urokinase-Type Plasminogen Activator Receptor (CD87) Activation of Plasminogen on Bacterial Surfaces Plasminogen Receptors on Eukaryotic Cells Plasminogen and Plasmin Vitronectin Plasminogen Activator Inhibitor 1 (PAI-1; SerpinE1) Plasminogen Activator Inhibitor- 2 (PAI-2; SerpinB2) Plasminogen Activator Inhibitor 3 (PAI-3) alpha2-Plasmin inhibitor (SerpinF2) Kallikrein in the Interstitial Space Kallikrein Plasma Kallikrein Tissue Kallikrein (KLK1) and Kallikrein-Related Peptidases Miscellaneous Observations on Kallikreins and Other Kinin-forming Enzymes in the Interstitial Space Hyaluronan and KLK1 Kinins Matrix Metalloproteinases in the Interstitial Space Matrix Metalloproteinases Activation of Matrix Metalloproteinases Membrane-Bound Matrix Metalloproteinases Matrix Metalloproteinases and Regulatory Proteolysis Matrix Metalloproteinases as Biopharmaceuticals Development of Inhibitors of Matrix Metalloproteinases for Therapeutic Use Substrate Specificity of Matrix Metalloproteinases. Tissue Inhibitors of Metalloproteinases (TIMPs) Chelation of Zinc Ions and Inhibition of Matrix Metalloproteinases. Compartmentalization and Regulation of Matrix Metalloproteinases. Coagulation Factors in the Interstitial Space Coagulation factors and their regulation in the interstitial space Coagulation Factors in Lymph and Interstitial Fluid Prothrombin Fibrinogen Fibrinogen and Hyaluronan Factor VII, Factor VIIa, and Tissue Factor Regulation of Tissue Factor in the Interstitial Space and Cryptic Tissue Factor Activity of Tissue Factor, Factor VII/VIIa, and Tissue Factor/Factor VIIa not Related to Blood Coagulation Factor VII and VIIa in the Interstitial Space Tissue Factor/Factor VIIa and Interstitial Pathology Tissue Factor/Factor VIIa and Tumor Development Intrinsic Coagulation Pathway in the Interstitium Factor IX Factor VIII and von Willebrand Factor Thrombin Formation of Thrombin in the Interstitial Space Factors Influencing the Activity of Thrombin in the Interstitial Space Effect of Hyaluronan on Thrombin Activity Substrates for Thrombin in the Interstitial Space The Role of Thrombin in Interstitial Fibrosis Protease Inhibitors in the Interstitial Space Proteolytic Regulation in the Interstitial Space Antithrombin Latent Antithrombin Plasminogen Activator Inhibitor-1 alpha1-Antitrypsin Heparin Cofactor II alpha2-Macroglobulin Tissue Inhibitors of Metalloproteinases (TIMPs)