Causes and pathogenesis of urolithiasis

There is no unified theory of the etiology of urolithiasis, since in each specific case it is possible to identify factors (or groups of factors) and diseases that have led to the development of metabolic disorders such as hyperuriculia, hypercalcuria, hyperoxaluria, hyperphosphaturia, changes in urinary acidification, and the occurrence of urolithiasis. In the occurrence of these metabolic shifts, some authors take the leading role exogenous factors, others - endogenous reasons.

Etiological factors of urolithiasis development

Endogenous factors		Exogenous factors
Hereditary	Acquired
Hereditary disorders of the urodynamics of the upper and / or lower urinary tract; Hereditary tubulopathies; Hereditary disorders in the activity of enzymes, hormones or vitamin deficiency / excess	Urinary system infection; Diseases of the digestive tract, liver and biliary tract; Congenital and acquired disorders of urodynamics of the upper and / or lower urinary tract; Prolonged or complete immobilization; Secondary disturbances of enzyme activity, Hormones or deficiency / excess vitamins; Secondary tubulopathies; Diseases leading to urolithiasis (osteoporosis, leukemia, bone metastases, multiple myeloma, etc.)	Climate; Geological structure of the soil; Chemical composition of water and flora; Food and drinking regimes of the population; Conditions of life and work, including environmental and occupational hazards; Iatrogenic factors

Pathogenesis of urolithiasis

Pathogenesis of urolithiasis is associated with one of three main hypotheses:

• enhanced precipitation-crystallization;
• matrix formation - nucleation;
• deficiency of crystallization inhibitors.

In the first hypothesis of precipitation-crystallization, the value of urine supersaturation is emphasized by crystalloids, which leads to their precipitation in the form of crystals. Such a mechanism obviously prevails in a number of cases (cystinuria, uraturia, triphylphosphate crystalluria, etc.). However, this can not explain the origin of oxalate-calcium stone formation, in which excretion of the main stone-forming components is practically not increased. In addition, a transient increase in the concentration of stone-forming compounds is possible, which can not always be captured.

The matrix hypothesis of stone formation is based on the assumption that a number of organic substances form the nucleus at first, on which further growth of the stone occurs as a result of the precipitation of crystals. To some substances, some authors include urinary microglobulin, collagen, mucoproteins, etc. Despite the fact that the urinary microglobulin is always found in the kidney stones, there is no evidence of its primary role in the formation of calculi. Urine can retain in the dissolved state a much larger amount of salts than aqueous solutions, due to the presence of inhibitors of crystal formation in it.

The third hypothesis relates the development of urolithiasis with the absence of inhibitors, even at normal concentrations of salts in the urine. However, there is no evidence of the absence of any one inhibitor in stone formation or a permanent deficiency of the main inhibitors of crystal formation in patients with urolithiasis.

These hypotheses of stone formation, undoubtedly, reflect some mechanisms of development of urolithiasis.

However, it is absolutely necessary to consider the pathogenesis of stone formation from the point of view of sources of origin of significant amounts of crystalloids, matrix substances, the causes of a decrease in the concentration of excreted urine inhibitors of crystal formation.

Increase of stone-forming substances in blood serum leads to an increase in their excretion by the kidneys - the main organ involved in maintaining homeostasis - and to urine oversaturation. In a supersaturated solution, the salts fall out in the form of crystals, which subsequently serves as a factor for the formation of microlites first, and then due to the settling of new crystals-urinary stones. However, urine is often supersaturated with salts (due to a change in the nature of nutrition, climatic conditions, etc.), but there is no formation of concrements. The presence of only one glut of urine is not enough to form a calculus. For the development of urolithiasis, other factors are necessary, such as a violation of urinary outflow, urinary tract infection, etc. In addition, substances that promote the maintenance of salts in dissolved form and prevent their crystallization are present in urine: citrate, magnesium ions, zinc, inorganic pyrophosphate, glycosaminoglycans, nephrocalcin, Tamma-Horswall protein, etc. Low concentration of citrate can be idiopathic or secondary (metabolic acidosis, potassium reduction, thiazide diuretics, decreased magnesium concentration, renal tubular acidosis, diarrhea). Citrate is freely filtered by the glomerulus of the kidneys and is 75% reabsorbed in the proximal-convoluted tubules. Most secondary causes lead to a decrease in the release of citrate in the urine due to increased reabsorption in the proximal-convoluted tubules.

[1], [2], [3], [4], [5], [6], [7], [8]