DISORDERS OF BODY-FLUID BALANCE - A NEW LOOK INTO THE MECHANISMS OF DISEASE

OBJECTIVE: To review the mechanisms of disease on the basis of dysfunc tion in body fluid distribution secondary to abnormalities in capillar y permeability and plasma membrane transport disorders, leading to qua ntitative and qualitative alterations of the interstitial space, a mai nly strategic compartment positioned between microcirculation and cell mass. DATA SOURCES: The recent literature on the mechanisms involved in the control of body fluid balance, with special reference to microc irculation and interstitial compartment physiology, as well as publish ed and unpublished original data from the authors' laboratory. DATA EX TRACTION AND SYNTHESIS: To illustrate the importance of capillary perm eability dysfunction in the development of disease, animal (rat and do g) models of chronic renal failure, acute diuretic-induced fluid deple tion, diabetes mellitus, arterial hypertension and ischemia-reperfusio n of the kidney were used in an attempt to show that in all these expe rimental models, basic capillary permeability dysfunction (measured by the extravasation of Evans blue, a marker of albumin leakage) develop s in specific microcirculation beds. As a consequence, tissue edema (i nterstitial and/or cellular) develops and likely impairs the traffic o f nutrients and waste products to and from the cellular mass, and/or c hallenges the microcirulation, leading to organ damage. Kidney dysfunc tion is measured by conventional clearance methods (renal hemodynamics and tubular function. In some models, the eventual mediators of vascu lar abnormality are examined by use of pharmacological tools. CONCLUSI ONS: The critical role of microcirculation dysfunctions, in particular capillary permeability, resulting in interstitial compositional chang es is presented as the basis of disease. The apparent specificity of t arget organ damage may represent the nonspecific result of physicochem ical alteration in the strategic interstitial fluid compartment.