Theoretical analysis of pathogenetic mechanisms in experimental acute renal failure

Theoretical analysis of pathogenetic mechanisms in experimental acute renal failure. A network thermodynamic model of glomerular dynamics has been employed to determine the degree of change in individual glomerular vascular resistances, hydraulic conductivity and proximal tubule pressure that, singly or in concert, could lower GFR to the degree expected in experimental acute renal failure (ARF). In both the rat and dog, the analysis shows that filtration failure is not achieved until preglomerular resistance (RA) is increased at least twofold or postglomerular resistance (RE) is decreased by 74% or more with all other determinants held at control values. Tubular obstruction alone will not provide failed filtration until tubule pressure is increased to 30 to 40mm Hg in the rat and 44mm Hg in the dog. A much smaller change in tubular pressure can contribute greatly to the development of filtration failure, however, when occurring in association with major change in individual vascular resistances. Glomerular capillary resistance must be increased to a value more than twice the normal sum of RA and RE (> fivefold in the dog), and glomerular capillary hydraulic conductivity lowered to below 5% of control, as isolated changes, before full filtration failure is approached. There is no reason to believe that most forms of ARF relate to only a single abnormality, however, and the effect of concomitant changes in individual resistances, hydraulic conductivity and proximal tubule pressure on glomerular filtration and blood flow is presented in the text and figures. A possible mechanism by which altered blood viscosity at the efferent arteriole may contribute to ARF is discussed and quantified. The degree of change in any determinant required to exert a given effect on filtration is independent of etiology, thus rendering the results of this analysis equally valid for any other pathological event which causes a significantly reduced GFR in the rat or dog. Analyse théorique des mécanismes pathogéniques dans l'insuffisance rénale aiguë expérimentale. Un modèle thermodynamique en réseau de la dynamique glomérulaire a été utilisé pour déterminer le degré de modification des résistances vasculaires glomérulaires, de la conductivité hydraulique et de la pression tubulaire proximale individuelles qui individuellement ou ensemble pourraient diminuer le débit de filtration glomérulaire au degré attendu dans l'insuffisance rénale aigüe expérimentale (ARF). Chez le rat et le ch