General Pathogenetic Factors
The development of nephrolithiasis is based on an imbalance between stone-forming substances and protective defense mechanisms. The primary initiating factor is urine supersaturation with salts. This process is promoted by a reduced urine output volume, shifts in acid-base balance (alterations in urinary pH), and the presence of bacterial flora.
Normally, salt precipitation is prevented by crystallization inhibitors: citrate, pyrophosphate, diphosphate, glycosaminoglycans, and a specific glycoprotein known as nephrocalcin. Their deficiency sharply increases the risk of crystallization. However, it is important to understand that metabolic abnormalities (such as hypercalciuria) do not guarantee the development of the disease, just as the absence of clear risk factors does not rule out lithiasis.
Classification of Calculi
All stones form on an organic mucoprotein framework upon which specific salts deposit. There are four main groups:
- Calcium stones (approx. 75%) — composed of pure calcium oxalate or a mixture with calcium phosphate.
- Struvite stones (approx. 15%) — composed of magnesium ammonium phosphate.
- Uric acid stones (approx. 6%) — composed of uric acid salts.
- Cystine stones (1–2%) — formed from the amino acid cystine.
Etiology of Specific Stone Types
- Calcium stones form due to various metabolic shifts. Isolated hypercalciuria without elevated blood calcium levels is detected in 55% of patients. Less commonly (approx. 5%), hypercalcemia resulting from hyperparathyroidism, diffuse bone diseases, or sarcoidosis is the cause. Hyperoxaluria plays a significant role: it can be primary (congenital) or enteral (due to excessive calcium absorption caused by small bowel disease or in vegetarians). Reduced citrate levels (hypocitraturia) associated with acidosis or chronic diarrhea also promote lithiasis. A specific variant is hyperuricosuric calcium nephrolithiasis, where uric acid crystals in the collecting ducts serve as a nidus that becomes coated with calcium oxalate.
- Struvite (infectious) stones are associated with urea-splitting bacteria (e.g., Proteus species and certain staphylococci). Urea is converted into ammonium, alkalinizing the urine, which induces the precipitation of magnesium ammonium phosphate. These calculi tend to grow rapidly and reach large sizes.
- Uric acid (urate) stones form in an acidic environment (pH 5.5) where uric acid is insoluble. Although they are associated with hyperuricemia (gout, leukemias), more than half of patients have completely normal blood uric acid levels. An important diagnostic detail: uric acid stones are radiolucent (invisible on plain abdominal radiographs), unlike radiopaque calcium stones.
- Cystine stones are the result of a genetically determined defect in the transport of cystine and other amino acids in the renal tubules.
Morphological Findings
The preferred sites for stone formation are the renal pelvis, calyces, and urinary bladder. Grossly, calculi vary significantly depending on their composition and the duration of the pathological process.
Numerous small formations 2–3 mm in diameter with smooth or spiky surfaces are frequently found in the renal pelvis. With prolonged, progressive salt precipitation, staghorn calculi develop — massive, branching structures that completely mirror the anatomical shape of the pelvicalyceal system, resembling deer antlers.