Regulatory Failure

Regulatory failure results in an oversecretion of hormones, leading to uremia by disruption of normal feedback mechanisms after renal failure. In response to the accumulation of ions and other waste products with ESRD, the maintenance of internal homeostasis is dependent on a variety of extrarenal processes. These homeostatic responses, while adaptive to one toxin, may have untoward effects outside the system they are attempting to regulate. The "trade-off" hypothesis, first proposed by Bricker, was initially postulated to explain how hyperparathyroidism in ESRD was a trade-off for the beneficial effects of high parathyroid hormone (PTH) levels on controlling phosphate levels. The trade-off for the maintenance of normal calcium and phosphate levels is hyperparathyroidism, causing increased bone turnover and leading to renal bone disease. Bricker has extended this trade-off hypothesis to sodium regulation in ESRD. As the glomerular filtration rate (GFR) decreases in ESRD patients, increasing fractional sodium excretion prevents salt retention. Bricker postulated that the trade-off for this natriuretic factor was a generalized inhibition of sodium transport, which he stated explained many aspects of uremic organ dysfunction.

While Bricker's trade-off hypothesis is still controversial, sodium transport abnormalities have been well documented in uremia. Na +, K+-ATPase activity is reduced in the red blood cells, leukocytes, intestinal epithelium, cardiac muscle, and skeletal muscle in uremic patients. Inhibition of Na +, K+-ATPase activity results in partial cellular depolarization and increased calcium entry, which are linked to both the high prevalence of hypertension and heart failure in ESRD. Recently an endogenous dialyzable digitalis-like inhibitor of Na +, K+-ATPase activity has been isolated in uremic plasma. This defect in Na+, K+-ATPase activity is reversed by dialysis. CLINICAL FEATURES

Uremia should only be viewed as a clinical syndrome; no single symptom, sign, or laboratory test is reliable in diagnosing all aspects of uremia. Although a correlation exists between the symptoms of uremia and a low GFR (8 to 10 mL/min), available laboratory tests [e.g., determinations of blood urea nitrogen (BUN) and creatinine] are inaccurate detecting trends in low GFR. The decision to start chronic dialysis is a clinical decision based on the symptoms of uremia ( T.aMe.„.8.9-1.).5

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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