A mathematical model of the rat kidney IV: whole-kidney response to hyperkalemia.
Academic Article
Overview
abstract
The renal response to acute hyperkalemia is mediated by increased K secretion within connecting tubule (CNT), flux that is modulated by tubular effects (e.g. aldosterone) in conjunction with increased luminal flow. There is ample evidence that peritubular K blunts Na reabsorption in proximal tubule, thick ascending Henle limb, and distal convoluted tubule (DCT). While any such reduction may augment CNT delivery, the relative contribution of each is uncertain. The kidney model of this lab was recently advanced with representation of cortical labyrinth and medullary ray. Model tubules capture the impact of hyperkalemia to blunt Na reabsorption within each upstream segment. However, this forces the question of the extent to which increased Na delivery is transmitted past macula densa and its tubuloglomerular feedback (TGF) signal. Beyond increasing macula densa Na delivery, peritubular K is predicted to raise cytosolic Cl and depolarize macula densa cells, which may also activate TGF. Thus, although upstream reduction in Na transport may be larger, it appears that the DCT effect is critical to increasing CNT delivery. Beyond the flow effect, hyperkalemia reduces ammoniagenesis and reduced ammoniagenesis enhances K excretion. What this model provides is a possible mechanism. When cortical NH4 is taken up via peritubular Na,K(NH4)-ATPase, it acidifies principal cells. Consequently, reduced ammoniagenesis increases principal cell pH, thereby increasing conductance of both ENaC and ROMK, enhancing K excretion. In this model, aldosterone's effect on principal cells, diminished DCT Na reabsorption, and reduced ammoniagenesis, all provide relatively equal and additive contributions to renal K excretion.
