Mechanism of Randall’s Plugs Development

Abstract

Mechanism of formation and development of intraluminal concretion, also called Randall's plug, extracted from a female patient forming calcium oxalate dihydrate (COD) calculi was examined. Some of these calculi were connected to the papillary tip, and had connections with the interior of the papilla with finger-like extensions in the collecting duct (CD). The intraluminal concretion consisted of inter-grown COD crystals of irregular size (30–100 μm), approximately 5% of biological hydroxyapatite (BHAP) and an organic matter. Urine of the patient was moderately supersaturated with respect to COD and amorphous calcium phosphate (ACP). Model of kidney, recently refined by Robertson, was used in calculations. Calculated Reynolds number indicated that the flow of liquid through tubules was purely laminar with parabolic velocity profile. COD crystals formed at the beginning of ascending loop of Henle by heterogeneous nucleation. Concentration of COD crystals in urine was limited and considered equal to concentration of crystals during crystaluria. The free particle and the fixed particle mechanisms were considered. The free particle mechanism assumes formation of a single crystal or agglomerate of crystals blocking the CD by virtue of size. The growth of COD crystals at concrete urinary supersaturation was too slow for a single crystal to attain size with settling velocity faster than the translation flow rate of liquid. Hydrodynamic shear caused aggregation of COD solid particles dispersed in a liquid flowing in the nephron. Number of COD crystals present in urine was not sufficient for formation of fractal agglomerate blocking the Bellini duct. Similarly, a fractal agglomerate of urinary phosphate present in the form of Posner's clusters was not large enough to obstruct the Bellini duct. The opening of the CD could not be obstructed by a single crystal of COD or fractal agglomerate composed of either COD crystals or calcium phosphate clusters, formed in urine by virtue of size. Solid objects not immobilised inside the CD were always washed out by urine flow from the CD of any orientation (also upward-draining CD). The formation and development of plug of our patient was explained by the fixed particle mechanism assuming that Randall's plug developes from crystal(s) attached directly to the tubule wall. The plug was modelled as concretion composed of successive layers of COD crystals originating on the top of underlying layer. When growth of a layer stopped, its surface was covered by organic matter that served as a substrate for nucleation of a new layer. The time of plug development was estimated as the time a COD crystal needed to reach the opposite side of the duct plus duration of interruptions of crystalline growth when plug surface was covered by a layer of organic matter and phosphatic particles were incorporated into concretion. The flux of Posner's clusters arriving to the concretion surface was estimated from theory of Brownian motion. These calculations suggested that obstruction of the Bellini duct of our patient by the Randall's plug occurred over a period of approximately 4 months after nucleus of concretion became attached to the duct wall or on the papillary tip.