Chronic Renal FailureThere are three major mechanisms that are involved in the pathogenesis of chronic renal failure: 1) decreased excretion of water and electrolytes; 2) decreased excretion of organic solutes (uremic toxins); and 3) decreased renal hormone synthesis. The kidney has a considerable physiologic reserve. Even with damage to ¾ of the total number of nephrons, the remaining ¼ are able to compensate and maintain balance. Effective compensation occurs until the GFR drops below 20% of normal. However, beyond this point the decreased Na+and water filtration causes edema and hyponatremia; the decreased K+secretion causes hyperkalemia; the decreased NH4+secretion causes a metabolic acidosis, and the decreased PO4-filtration causes hyperphosphatemia. The buffering of the acidosis by bone and skeletal muscle results in osteopenia and a loss of lean body mass and muscle weakness. The first defect in the cascade of pathophysiological events is phosphate retention when the GFR declines to 50-60 ml/min.
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