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Concrement-forming substances (^A1) can reach concentrations in the urine that lie above their solubility threshold. In the so-called metastable range the formation of crystals may not occur at all, or only slowly, despite supersaturation of the solution. However, when the concentrations rise beyond the metastable range, crystallization occurs. Dissolving already formed crystals is possible only by reducing the concentration to below the metastable range.

The most frequently found components in kidney stones are calcium oxalate (ca. 70%), calcium phosphate or magnesium-ammonium phosphate (ca. 30%), uric acid or urate (ca. 30%) as well as xanthine or cystine (< 5 %). Several substances may be contained in one stone, because crystals that have already formed act as nuclei for crystallization and facilitate the deposition of other metastably dissolved substances (hence the total is > 100%).

Certain substances that form complexes, such as citrate, pyrophosphate, and (acid) phosphate, can bind Ca2+ and, by reducing the Ca2+ concentration, are able to prevent calcium phosphate and calcium oxalate from precipitating.

Causes of stone formation. The raised concentration of stone-forming substances can be the result of prerenal, renal, and postrenal factors:

Prerenal causes produce the increased filtration and excretion of stone-producing substances via a raised plasma concentration (^p. 94). Thus, prerenal hypercalciuria and phosphaturia are the result of raised intestinal absorption or mobilization from bone, for example, if there is an excess of PTH or calcitriol (^A2). Hyperoxalemia can be brought about by a metabolic defect in amino acid breakdown or by increased intestinal absorption (^A3). Hyperuricemia occurs as a result of an excessive supply, increased new synthesis, or increased breakdown of purines (^A3). Xanthine stones may occur when the formation of purines is greatly increased and the breakdown of xanthines to uric acid is inhibited. However, xanthine is much more soluble than uric acid and xanthine stones are therefore much less common.

Abnormal renal reabsorption is a frequent cause of increased renal excretion in hypercal-ciuria and an invariable cause in cystinuria (^ p. 96). The Ca2+ concentration in blood is then maintained by the intestinal absorption and mobilization of bone minerals, while the cystine concentration is maintained by a reduced breakdown.

Release of ADH (in volume depletion, stress, etc.; ^ p. 260) leads to a raised concentration of stone-forming substances via enhanced urine concentration (^ A4).

The solubility of some substances depends on the pH of urine. Phosphates are easily dissolved in an acidic urine, but poorly in an alkaline one. Phosphate stones are therefore, as a rule, only found in alkaline urine. Conversely, uric acid (urate) is more soluble when dissociated than undissociated, and uric acid stones are formed more readily in acidic urine. If the formation of NH3 is reduced, the urine has to be more acidic for acid to be eliminated, and this promotes the formation of urate stones.

A significant factor is also how long crystals that have already formed actually remain in the supersaturated urine. The length of time depends on the diuresis and the flow conditions in the lower urinary tract that can, for example, lead to crystals getting caught (postre-nal cause).

The effect of urolithiasis is that it blocks the lower urinary tract (^A5). In addition, stretching of the ureteric muscles elicits very painful contractions (renal colic). Obstruction to flow leads to ureteral dilation and hydrone-phrosis with cessation of excretion. Even after removal of a stone, damage to the kidney may persist. The urinary obstruction also promotes growth of pathogens (urinary tract infection; pyelonephritis; ^ p. 106). Urea-splitting pathogens form NH3 from urea, thus alkalinizing the urine. This in turn, in a vicious circle, favors the formation of phosphate stones. Even without bacterial colonization, intrarenal deposition of uric acid (gouty kidney) or of calcium salts (nephrocalcinosis) can result in inflammation and destruction of renal tissue.


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