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The functional renal failure accompanying advanced liver disease is characterized by azotemia, a urine of very low sodium concentration and systemic hypotension with decreased renal perfusion and high renal vascular resistance. Patients with this disorder have a markedly reduced ability to excrete free water and develop hyponatremia, ascites and edema. It is postulated that this renal dysfunction is due to hepatic failure to make renin substrate. Renin released from the kidney is thus unable to exert its pressor effect. The resultant hypotension and renal hypoperfusion continue to stimulate excessive synthesis and release of renin. It is postulated that the overdriven renal renin system increases renovascular resistance at the level of the glomerular arterioles. This causes decreased renal blood flow and decreased glomerular filtration rate leading to salt and water retention and azotemia. Since no renin substrate is available for human infusion, this hypothesis could be tested either by infusion of angiotensin II to restore systemic blood pressure and renal perfusion or by beta adrenergic blockade with propranolol to attempt to decrease the intrarenal effects of renin, restore glomerular blood flow and filtration and thus return of renal function.

A new three barrier, four compartment model for sodium transport in high resistance urinary epithelia is presented. This model provides a unified and simplified mechanistic explanation for sodium transport and its quantitative regulation. Sodium enters the epithelial cell by passive diffusion. Active extrusion occurs across the lateral cell membrane into the lateral intercellular space (LICS). Sodium movement from the LICS into the serosal compartment is not free and unobstructed as in the models for low resistance epithelia, but rather occurs through a regulatory channel of the LICS passing through desmosomes and the basilar slit. The exact configuration of this regulatory channel controls the rate of sodium movement from the LICS into the serosal compartment. Thus, the configuration of the regulatory channel controls the afterload on the sodium pump and thus ultimately controls the rate of transepithelial sodium transport. Antidiuretic hormone could act by increasing the effective width of this regulatory channel by contraction of intracellular microtubules or microfilaments. Present theories for regulation of transepithelial sodium transport in high resistance epithelia invoke a regulatory barrier at the apical cell membrane or at the active sodium pump located in the basolateral cell membrane. The hypothetical model presented here invokes a new alternative: regulation of the active pump rate by the sodium concentration in the LICS serving as an afterload on the pump; sodium escape from the LICS into the serosal compartment thus becomes the regulatory step for transepithelial transport.

It is theoretically inappropriate to characterize an actively transporting epithelim by "resistance" alone which is correctly applied only to passive circuit elements. Rather, such epithelia (if they actively transport sodium) required, as a minimum, characterization by an active circuit element parameter such as voltage (E Na), current (I Na) or power (WNa) in some configuration with resistances. Recent experimental studies of epithelia which actively transport sodium have omitted consideration of the active circuit element and attributed all measured changes observed to "resistance" changes in the epithelium as the transepithelial sodium gradient is altered. It is suggested that the observed changes in voltage/current ratio could be consequences of changes in the electrical behavior of the active circuit element of such epithelia. It may be biologically impossible to suppress all electromotive forces in epithelia to measure the truly passive characteristics of the epithelim without destroying tissue viability. The actual methods used to date for measurement of "resistance" in epithelia consist of perturbing signals which might alter the electrical behavior of an active element such as an "ion pump"; the observed changes in voltage to current ratio observed in such experiments can be better explained by a change in the active ion pump rather than by changes in passive epithelial "resistance".