Can Randall's plug composed of calcium oxalate form via the free particle mechanism?

BACKGROUND: The likelihood of a Randall's plug composed of calcium oxalate monohydrate (COM) forming by the free particle mechanism in a model of kidney with a structure recently described by Robertson was examined at the most favourable conditions for the considered mechanism. METHODS: The Robertson model of the kidney is used in the following development. The classical theory of crystallization was used for calculations. RESULTS: Initial COM nuclei were assumed to form at the beginning of the ascending loop of Henle where the supersaturation with respect to COM has been shown to reach the threshold level for spontaneous nucleation. Nucleation proceeds by a heterogeneous mechanism. The formed particles are transported in the nephron by a laminar flow of liquid with a parabolic velocity profile. Particles travel with a velocity dependent on their position in the cross-section of the nephron assumed to be straight tubule with smooth walls and without any sharp bends and kinks. These particles move faster with time as they grow as a result of being surrounded by the supersaturated liquid. Individual COM particles (crystals) can reach maximum diameter of 5.2 × 10-6 m, i.e. 5.2 µm, at the opening of the CD and would thus always be washed out of the CD into the calyx regardless of the orientation of the CD. Agglomeration of COM crystals forms a fractal object with an apparent density lower than the density of solid COM. The agglomerate that can block the beginning of the CD is composed of more crystals than are available even during crystaluria. Moreover the settling velocity of agglomerate blocking the opening of the CD is lower than the liquid flow and thus such agglomerate would be washed out even from upward-draining CD. CONCLUSIONS: The free particle mechanism may be responsible for the formation of a Randall's plug composed by COM only in specific infrequent cases such as an abnormal structure of kidney. Majority of incidences of Randall's plug development by COM are caused by mechanism different from the free particle mechanism.

Estructura ultrafina de cálculos renales de oxalato cálcico monohidrato / Ultrafine structure of calcium oxalate monohydrate renal calcul

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Structural features of three ureterocele calculi.

Ureterocele calculi are developed in cavities with urinary retention but far from the upper renal cavities. The structural features of three ureterocele calcium oxalate stones were observed by scanning electron microscope coupled with X ray microanalysis. The urinary parameters of the three patients were also determined. The stone A consisted of loose structure of large calcium oxalate dihydrate crystals and small spheres of hydroxyapatite. The interior contains disorganized plate-like calcium oxalate monohydrate crystals. The stone B was formed by a compact outer layer of calcium oxalate monohydrate columnar crystals. The structure of stone interior was similar to the stone A. The stone C was formed by concentric layers composed of either calcium oxalate monohydrate columnar crystals or hydroxyapatite. The core consisted of agglomerated calcium oxalate monohydrate crystals, hydroxyapatite and organic matter. From the urinary biochemical data it was deduced that two ureterocele patients (who formed A and B stones) were hypercalciuric (calcium > 300 mg/24 h), being 6.5 the urinary pH value of the patient that formed the A stone, and 7.0 the urinary pH of the patient that formed the C stone. The rest of urinary parameters for the three patients were normal. Thus, one of the requisite conditions for unattached stone development is the existence of a place inside the urinary tract where the solid particles that act as calculus initiator of the stone can be retained enough time to exert this action.

Study on concretions developed around urinary catheters and mechanisms of renal calculi development.

AIMS: To study the structure and composition of encrustation and concretions developed on urinary catheters to better understand their formation mechanism to be able to prevent them. METHODS: The surface of catheters was studied by direct and scanning electron microscopy observation. In vitro formation of encrustations was performed in synthetic urine. RESULTS: The surface of catheters was covered by a continuous layer of organic matter, on which a thin scale consisting of crystals of calcium oxalate monohydrate (COM), uric acid anhydrous or calcium phosphate developed. Encrustations observed on catheters generally exhibited the same composition as the previously developed renal calculi. In catheters collected from patients without previous episodes of renal calculi or with previous episodes of infected renal calculi in which infection was afterwards eradicated, on the first organic layer, in that case plate-like COM crystals forming a columnar layer were observed. In vitro experiments demonstrated that COM columnar structures were only formed when normocalciuric urine containing organic matter was used, and the presence of crystallization inhibitors, as phytate, notably delayed their formation. CONCLUSION: Calcium oxalate was the main crystalline phase developed on catheters inserted in patients, specially in the absence of urinary infection or urinary pH values <5.5 and high urinary uric acid levels. Thus, prophylaxis of encrustations may consist of preventive measures usually applied in cases of recurrent idiopathic calcium oxalate urolithiasis.

Uric acid calculi: types, etiology and mechanisms of formation.

The study of the composition and structure of 41 stones composed of uric acid was complemented by in vitro investigation of the crystallization of uric acid. Uric acid dihydrate (UAD) precipitates from synthetic urine under physiological conditions when the medium is supersaturated with respect to this compound, though uric acid anhydrous (UAA) represents the thermodynamically stable form. Solid UAD in contact with liquid transforms into UAA within 2 days. This transition is accompanied by development of hexagonal bulky crystals of UAA and appearance of cracks in the UAD crystals. Uric acid calculi can be classified into two groups, differing in outer appearance and inner structure. Type I includes stones with a little central core and a compact columnar UAA shell and stones with interior structured in alternating densely non-columnar layers developed around a central core; both of them are formed mainly by crystalline growth at low uric acid supersaturation. Type II includes porous stones without inner structure and stones formed by a well developed outermost layer with an inner central cavity; this type of stones is formed mainly by sedimentation of uric acid crystals generated at higher uric acid supersaturation.

Renal stone formation and development.

A concise account of formation mechanisms of attached (papillary) and unattached renal stones is presented. Urinary conditions prevailing at least during the stone forming period are indicated. Ten main categories of renal stones, covering over 95% of all conceivable calculi, are distinguished based on their composition and structure. Aetiologic factors leading to stone formation of every category are specified and general outlines of recommended treatment procedures indicated.

Structure of uric acid concretion developed around a catheter.

A uric acid concretion formed round a catheter (JJ stent) in the bladder and removed intact from the body together with the catheter was studied using an electron scanning microscope. The concretion was composed of anhydrous uric acid, some uric acid dihydrate (< 5 wt.%) and individual particles of calcium oxalate monohydrate. The stone interior was porous with frequent occurrence of differently sized cavities that were either empty or partially filled with particles of uric acid and/or calcium oxalate monohydrate. Calcium oxalate particles were not of crystalluria origin but developed in the cavity. The succession of processes leading to the stone formation was deduced from its inner structure. The stone was formed due to a crystalline growth with minor, if any, participation of sedimentation. The estimated average rate of the calculus development, 2 x 10(-9) m/s, confirms the predominant role of crystalline growth in stone formation and indicates a relatively low urinary supersaturation with respect to uric acid prevailing during the period of calculogenesis.

Phosphates precipitating from artificial urine and fine structure of phosphate renal calculi.

Phosphates precipitating from artificial urine in the pH range 6-8 were identified using X-ray diffraction, chemical analysis and scanning electron microscopy. The influence of magnesium and citrate on phases precipitating from urine was established. From urine containing a normal quantity of magnesium (around 70 ppm), brushite accompanied by hydroxyapatite (HAP) precipitated at pH < or = 7.0 and struvite with HAP at pH > 7.0. HAP was formed exclusively from magnesium deficient urine at pH 7.0. Newberyite, octacalcium phosphate and whitlockite were not identified. The chemical and phase composition and inner fine structure of 14 phosphate calculi were studied. Three types of stones were distinguished based on their magnesium content: (i) stones rich in magnesium composed of struvite, hydroxyapatite and abundant organic matter, (ii) stones with low magnesium content constituted by calcium deficient hydroxyapatite, up to 5% of struvite, considerable amount of organic matter and occasionally brushite, and (iii) calculi without magnesium consisting of brushite, hydroxyapatite and little organic matter. Conditions prevaling during stone-formation assessed for each type of stone were confirmed by corresponding urinary biochemical data and corroborate the in vitro studies of phosphates precipitation.

Study on calcium oxalate monohydrate renal uroliths. I. Qualitative properties.

Shape, colour, surface features and external appearance were determined from 33 human uroliths composed predominantly of calcium oxalate monohydrate (COM). Based on these properties COM renal stones were classified into mulberry (M) and spheroid (S) type, each of which was further divided into two well defined subtypes, M1-fused globules, M2-loose globules, S1-corrugated surface and S2-even surface. This classification indicates that only specific combinations of external characteristics could occur on COM renal uroliths. No apparent correlation between the stone type and respective biochemical urinary data transpired from available information.

A study on calcium oxalate monohydrate renal uroliths. II. Fine inner structure.

The inner fine structure of 30 human uroliths composed predominantly of calcium oxalate monohydrate was studied in detail. Each type of stone distinguished on the basis of qualitative parameters, viz. M1, M2, S1 and S2 (see Part I), exhibited a specific and characteristic inner structure different in several well-defined aspects from the other types. The inner structure suggests a sedimentary origin of the M1 type stone whereas the fixed particle origin of the M2, S1 and S2 stones, 3 types of core on which M2, S1 and S2 calculi developed were identified. The A type was represented by a void cavity with walls covered by an organic matter, the B type was formed by loosely arranged COM crystals and the C type was represented by a layer of an organic matter. Clinical observations lend support to the sedimentary origin of the M1 stones.

Study on calcium oxalate monohydrate renal uroliths. III. Composition and density.

Density and content of mineral constituents were determined for 33 human calcium oxalate monohydrate (hereafter COM) uroliths whose external appearance and inner structure were described in part I and II respectively. Studied stones contained 0.13-0.42 wt.% of struvite, 0.68-4.12 wt.% of hydroxyapatite, 73-96 wt.% of COM and 3-10 wt.% of water unbound in a crystallohydrate 10 to 20 wt.% of calculus mass is not accounted for by chemical analysis. Density of COM calculi varying between 1.67 and 2.06 g cm-3 is not a function of any single stone parameter. Around 30% of stone volume is not occupied by crystalline components. The mulberry stones of sedimentary origin contained higher amount of organic matter than papillar and mulberry stones displaying site of attachment to epithelium.

Calcium oxalate monohydrate renal calculi. Formation and development mechanism.

Available information relevant to stone genesis on both calcium oxalate monohydrate crystallization and fine inner structure of papillary calculi is reviewed. Integration of attained facts facilitated formulating a feasible mechanism of papillary calculi formation and development. Medical implications of this mechanism are assessed.

Role of agglomeration in the early stages of papillar stone formation.

Possible effects of crystal agglomeration on the early stages of calcium oxalate papillar stone formation are evaluated. The collecting ducts are filled with liquid that flows laminarly as established through hydrodynamical and physicochemical considerations. Under such conditions, agglomeration due to laminar shear forces proceeds. Agglomeration of calcium oxalate monohydrate crystals present in urine at a concentration typical for clinically observed crystalluria cannot result in the formation of a particle sufficiently large enough to be retained in the Bellini's duct and become a papillar stone nidus (nucleus). Formation of such an aggregate during the passage time of urine through the duct requires an unrealistically high concentration of crystals in urine, one that exceeds the normal content of urinary oxalate by several orders of magnitude. Aggregates obstructing the Bellini's duct as assumed in the free particle theory cannot represent a major factor in stone formation. This conclusion is corroborated by experimental results and other observations.

Experimental technique simulating oxalocalcic renal stone generation.

A new technique simulating some of the conditions experienced by papillar and caliceal oxalocalcic stones during the early stages of their generation was developed. This technique enables the study of how conditions prevailing at calculogenesis, such as pH, composition of urine and presence of admixtures, influence the rate of formation and development, the crystalline texture and the composition of the concretion formed. Results achieved with this technique demonstrate that: (1) an appropriate substrate always gives rise to a crystalline concretion if it is in contact with supersaturated urine; (2) primary agglomeration plays a significant role in concretion development whereas secondary agglomeration is of minor importance; and (3) citrate and pyrophosphate exert a considerable influence on the shape and composition of particles constituting the concretion.

Mechanism of oxalocalcic renal calculi generation.

Based on reconsideration of the contemporary knowledge on calcium oxalate urolithiasis a feasible mechanism of calculi generation is suggested. Experimental findings and clinical aspects supporting the suggested mechanism are presented. The ways of urolithiasis treatment and areas of future research are indicated.

Artificial simulation of renal stone formation. Influence of some urinary components.

The effect of natural admixtures occurring in human urine (citrate, pyrophosphate and glycosaminoglycans) on the precipitation of stone-forming compounds was studied. Experiments were carried out under conditions closely simulating the early stages of renal stone formation. Among the studied admixtures, citrate was determined as the most effective substance preventing the phosphate particle formation. Indeed, in the presence of citrate, some calcium oxalate monohydrate crystals were found. Pyrophosphate induced the formation of calcium oxalate dihydrate crystals. Phosphate crystals appeared at pH 6 and never at pH 5. The easy formation of phosphate particles supports the hypothesis that these crystals represent a very important heterogeneous nucleus-initiating oxalocalcic calculus formation in the kidney. Reported results also indicated uric acid as a significant heterogeneous nucleus of calcium oxalate monohydrate crystals at urinary pH equal or lower than 5 and the important role of bacteria in increasing the organic detritus deposited on the solid surfaces.

Fine structure of calcium oxalate monohydrate renal calculi.

Fine structure, location and size of the core of 12 calcium oxalate monohydrate (COM) papillar calculi from different 'idiopathic' stone-formers were studied by an optical and scanning electron microscope equipped with the EDAX analytical device. Each individual core exhibited a unique overall structure composed of loosely arranged twined and intergrown crystals of plate-like and/or columnar shape and particles of 'rosette' structure with considerable void space among crystals in some cases or compact structure in others. Crystals were covered by a thin layer or organic material mostly invisible to the microscope. Sometimes debris of organic origin in a core was observed. A substantial amount of organic matrix appeared at the core boundary, often in the form of amorphous plates. The outer striated layer of COM stone consisting of tightly packed columnar crystals originated on this matrix. The stone core was located near the stone surface that was attached to the kidney wall and contained foreign particles that act as heterogeneous nucleants of calcium oxalate crystals.

Agglomeration of calcium oxalate monohydrate in synthetic urine.

The development of agglomerated particles of calcium oxalate monohydrate (COM) on the semi-batch precipitation from a synthetic urine carried out at physiological conditions (37 degrees C, pH = 5.5) was studied by optical and electron scanning microscopy. COM agglomerates develop by primary and secondary agglomeration proceeding simultaneously; the latter mechanism is, however, less important than the former. Citrate ions modify slightly the COM crystal shape and inhibit primary agglomeration. Mucin particles serve as a substrate for preferential formation (nucleation) of new COM crystals. The structure of formed agglomerates closely resembles that of a certain type of COM renal calculi. A combination of primary agglomeration of crystals forming stones and nucleation of new crystals on a mucoprotein layer partially covering their surface constitutes the possible mechanism of such stone development. Experimental data support this mechanism.