Small crystals formed in the kidney. The most common crystals are made of calcium oxalate and they are generally 4–5 mm. Staghorn kidney stones are considerably larger. 1. Calcium and oxalate come together to make the crystal nucleus. Supersaturation promotes their combination (as does inhibition.) 2. Continued deposition at the renal papillae leads to the growth of the kidney stones. 3. Kidney stones grow and collect debris. In the case where the kidney stones block all routes to the renal papillae, this can cause extreme discomfort and pain. 4. The complete staghorn stone forms and retention occurs. Smaller solids that break off can become trapped in the urinary glands causing discomfort. 5. Displaced stones travel through the ureter. If they cannot be broken down, they must be physically removed by a surgeon. Supersaturation of urine When the urine becomes supersaturated (when the urine solvent contains more solutes than it can hold in solution) with one or more calculogenic (crystal-forming) substances, a seed crystal may form through the process of nucleation. Heterogeneous nucleation (where there is a solid surface present on which a crystal can grow) proceeds more rapidly than homogeneous nucleation (where a crystal must grow in a liquid medium with no such surface), because it requires less energy. Adhering to cells on the surface of a renal papilla, a seed crystal can grow and aggregate into an organized mass. Depending on the chemical composition of the crystal, the stone-forming process may proceed more rapidly when the urine pH is unusually high or low. Supersaturation of the urine with respect to a calculogenic compound is pH-dependent. For example, at a pH of 7.0, the solubility of uric acid in urine is 158 mg/100 ml. Reducing the pH to 5.0 decreases the solubility of uric acid to less than 8 mg/100 ml. The formation of uric-acid stones requires a combination of hyperuricosuria (high urine uric-acid levels) and low urine pH; hyperuricosuria alone is not associated with uric-acid stone formation if the urine pH is alkaline. Supersaturation of the urine is a necessary, but not a sufficient, condition for the development of any urinary calculus. Supersaturation is likely the underlying cause of uric acid and cystine stones, but calcium-based stones (especially calcium oxalate stones) may have a more complex cause. Randall's plaque While supersaturation of urine may lead to crystalluria, it does not necessarily promote the formation of a kidney stone because the particle may not reach the sufficient size needed for renal attachment. On the other hand, Randall's plaques, which were first identified by Alexander Randall in 1937, are calcium phosphate deposits that form in the papillary interstitium and are thought to be the nidus required for stone development. In addition to Randall's plugs, which form in the Duct of Bellini, these structures can generate reactive oxygen species that further enhance stone formation. Pathogenic bacteria Some bacteria have roles in promoting stone formation. Specifically, urease-positive bacteria, such as Proteus mirabilis can produce the enzyme urease, which converts urea to ammonia and carbon dioxide. This increases the urinary pH and promotes struvite stone formation. Additionally, non-urease producing bacteria can provide bacteria components that can promote calcium oxalate crystallization, though this mechanism is poorly understood. Inhibitors of stone formation Normal urine contains chelating agents, such as citrate, that inhibit the nucleation, growth, and aggregation of calcium-containing crystals. Other endogenous inhibitors include calgranulin (an S-100 calcium-binding protein), Tamm–Horsfall protein, glycosaminoglycans, uropontin (a form of osteopontin), nephrocalcin (an acidic glycoprotein), prothrombin F1 peptide, and bikunin (uronic acid-rich protein). The biochemical mechanisms of action of these substances have not yet been thoroughly elucidated. However, when these substances fall below their normal proportions, stones can form from an aggregation of crystals. Sufficient dietary intake of magnesium and citrate inhibits the formation of calcium oxalate and calcium phosphate stones; in addition, magnesium and citrate operate synergistically to inhibit kidney stones. The efficacy of magnesium in subduing stone formation and growth is dose-dependent. Hypocitraturia Hypocitraturia or low urinary-citrate excretion (defined as less than 320 mg/day) can cause kidney stones in up to 2/3 of cases. The protective role of citrate is linked to several mechanisms; citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. Therapy with potassium citrate or magnesium potassium citrate is commonly prescribed in clinical practice to increase urinary citrate and to reduce stone formation rates.
complications of Hypercalcaemia
medical cause of Hypercalcaemia
complications of Hyperkalemia
complications of Hypophosphatemia
medical cause of Hyperphosphatemia
medical cause of Hyperkalemia
complications of Osteoporosis
complications of Hyperparathyroidism