Pathophysiology
Summary
Renal stones mainly form due to renal tubular supersaturation, with hydration being the mainstay of prevention. The most prevalent are calcium oxalate stones, often arising from metabolic abnormalities like hypercalciuria with normocalcemia. This hypercalciuria can stem from three main sources: excessive gut absorption (absorptive), proximal tubule reabsorption defects (renal), and bone resorption (resorptive).
Metabolic and dietary factors can play a significant role in the formation of calcium oxalate and calcium phosphate stones. For example, acidosis leads to hypocitraturia, facilitating calcium stones. Diarrhea exacerbates this by causing fluid loss and acidemia when severe.
Dietary factors also play a role: high-protein diets cause acidemia and hypocitraturia, while high-sodium diets impair the reabsorption of sodium and calcium in the nephron, both of which promote calcium stone formation. Moreover, low dietary calcium and fat malabsorption conditions can enhance GI absorption of unbound oxalate, increasing the risk of calcium oxalate stone formation.
Calcium phosphate stones are more common in children, and are often associated with type 1 renal tubular acidosis and an alkaline urine environment. Microscopically, calcium oxalate stones exhibit an ‘envelope’ shape, while calcium phosphate stones show an ‘elongated-wedge’ shape. If indicated, hydrochlorothiazide can be employed to increase reabsorption of calcium in the distal tubule as a preventative measure.
Lesson Outline
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FAQs
Several metabolic conditions can contribute to the development of these stones. These include hypercalciuria (idiopathic, hypercalcemia chronic acidosis), absorptive hypercalciuria caused by excessive gut absorption of calcium, renal hypercalciuria resulting from a defect in proximal reabsorption of calcium, and resorptive hypercalciuria caused by increased resorption of calcium from bone. Acidosis can also increase the risk of calcium stone, as acidemia promotes the dissolution of calcium phosphate from bone into the bloodstream, which is then filtered through the kidneys and into the urine, contributing to hypercalciuria. Hypocitraturia induced by acidemia also contributes to calcium stones.
Diet can play a significant role in the formation of calcium oxalate and calcium phosphate stones. For example, diets high in protein can contribute to the formation of calcium stones by inducing acidemia, which lowers citrate levels and disrupts the calcium-phosphate buffer system. Elevated sodium intake can cause calcium stones by impairing the reabsorption of both sodium and calcium in the nephron, thereby increasing urinary calcium levels. Moreover, low dietary calcium intake and fat malabsorption conditions can enhance GI absorption of unbound oxalate, increasing the risk of calcium oxalate stones.
The formation of calcium oxalate and calcium phosphate stones involves different mechanisms and predisposing factors. Calcium oxalate stones are primarily the result of elevated levels of calcium and oxalate in the renal tubules. Excess intake of oxalate-rich foods, low fluid intake, or intestinal malabsorption may contribute to high oxalate concentrations. On the other hand, calcium phosphate stones are often associated with type 1 renal tubular acidosis, which leads to an alkaline urinary pH. This alkaline environment is conducive to the precipitation of calcium phosphate crystals. Calcium phosphate stones are more commonly seen in children, while calcium oxalate stones are the most frequent type in adults.
Citrate acts as a natural inhibitor of calcium stone formation by binding to calcium in the renal tubules. This soluble complex prevents the supersaturation of calcium, thereby reducing the likelihood of stone formation. Acidic conditions, however, can lead to hypocitraturia, or low citrate levels, which diminishes this protective effect and promotes calcium stone formation.
The gastrointestinal system can be a significant contributor to calcium oxalate stone formation. For instance, conditions that cause fat malabsorption, such as Crohn's disease and short bowel syndrome, can lead to calcium binding with unabsorbed fatty acids in the gut. This results in elevated levels of free oxalate being absorbed into the bloodstream. Similarly, a purely vegan diet without adequate calcium supplementation can also enhance gastrointestinal absorption of oxalate, increasing the risk of stone formation.
