Disorders of body fluid balance: a new look into the mechanisms of disease.
OBJECTIVE
To review the mechanisms of disease on the basis of dysfunction in body fluid distribution secondary to abnormalities in capillary permeability and plasma membrane transport disorders, leading to quantitative and qualitative alterations of the interstitial space, a mainly strategic compartment positioned between the microcirculation and cell mass.


METHODS
The recent literature on the mechanisms involved in the control of body fluid balance, with special reference to microcirculation and interstitial compartment physiology, as well as published and unpublished original data from the authors laboratory.


METHODS
To illustrate the importance of capillary permeability dysfunction in the development of disease, animal (rat and dog) models of chronic renal failure, acute diuretic-induced fluid depletion, diabetes mellitus, arterial hypertension and ischemia-reperfusion of the kidney were used in an attempt to show that in all these experimental models, basic capillary permeability dysfunction (measured by the extravasation of Evans blue, a marker of albumin leakage) develops in specific microcirculation beds. As a consequence, tissue edema (interstitial and/or cellular) develops and likely impairs the traffic of nutrients and waste products to and from the cellular mass, and/or challenges the microcirculation, leading to organ damage. Kidney dysfunction is measured by conventional clearance methods (renal hemodynamics and tubular function). In some models, the eventual mediators of vascular abnormality are examined by use of pharmacological tools.


CONCLUSIONS
The critical role of microcirculation dysfunctions, in particular capillary permeability, resulting in interstitial compositional changes is presented as the basis of disease. The apparent specificity of target organ damage may represent the nonspecific result of physicochemical alteration in the strategic interstitial fluid compartment.
Plante
G E
GE
Department of Medicine, University of Sherbrooke, Quebec.
Chakir
M
M
Lehoux
S
S
Lortie
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001826:Body Fluids / Q000502:physiology; D002199:Capillary Permeability; D002316:Cardiotonic Agents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D004232:Diuretics / Q000494:pharmacology; D004285:Dogs; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007511:Ischemia; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D012079:Renal Circulation; D014883:Water-Electrolyte Imbalance / Q000503:physiopathology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D004232:Diuretics; D010042:Ouabain