Stone formation pathophysiology
A salt solution is considered saturated when no more added salt crystals will dissolve – this concentration level is the solubility product
Despite concentrations of salts exceeding the solubility product in urine, crystallisation doesn’t always occur, because of the presence of stone inhibitors – this is the metastable state.
As the concentration further increases it reaches the formation product – where the salt can no longer be held in solution, and crystals form.
Therefore there are three states of saturation – undersaturated, metastable and unstable.
Nuclei are the earliest crystal structures which don’t dissolve.
Heterogenous nucleation is the formation of nuclei onto different surfaces – epithelial cells, cell debris, other crystals – occuring the metastable zone.
Homogenous nucleation is the formation of crystals in pure solution – occuring in the unstable zone.
Epitaxy is the formation of crystals on other crystal types.
Stone inhibitors may nuclei unstable and prevent crystallisation.
In the metastable state, there is a constant ‘tug of war’ between crystallisation and solution.
Stone formation theories
Free particle growth
Crystals or nuclei form de novo in supersaturated urine while passing through the nephron, to a critical mass which gets ‘stuck’
Fixed particle growth
Crystals bind to an anchoring site, and are then exposed to the supersaturated urine for a longer time. Anchoring sties thought to be sites of cellular injury or debris, Randall’s plaques, nanobacteria and nanoparticles.
Randall plaques
Sub-theory of fixed particle theory – plaques are subepithelial flecks of calcium phosphate formed at the loop of Henle, which erupt through the papillary epithelium – being exposed to supersaturated urine and undergoing nucleation and epitaxy at the tip of the papilla.
