Serum phosphate, rise

In the absence of PTH (idiopathic or surgical hypoparathyroidism) or an abnormal target tissue response to PTH (pseudohypoparathyroidism), serum calcium falls and serum phosphate rises. In such patients, l,25(OH)2D levels are... 

Because the kidney is the only significant source of la-OHase, inadequate formation of l,25-(OH)2D3 occurs in renal failure [168], Not only is the mass of kidney tissue and therefore of enzyme decreased, but also with renal failure, phosphate excretion is reduced and serum phosphate rises. Increased phosphate inhibits la-OHase so that little l,25-(OH)2D3 is formed. Acidosis, a frequent result of renal failure, also impairs la-OHase activity [169, 170]. Deficiency of the active form of vitamin D causes osteomalacia, a prominent feature of renal osteodystrophy. Therapy is directed toward use of l,25-(OH)2D3, reduction of serum phosphate, and correction of acidosis, so that residual la-OHase can be expressed. 

Thus, a complex relationship exists among serum Ca + and phosphate, PTH, and vitamin D and its metabolites. Release of PTH in response to low serum Ca + directly mobilizes calcium from bone and increases synthesis of 1, 25-(0H)2D, which in turn mobilizes skeletal Ca + and causes increased intestinal calcium absorption. These effects raise the serum Ca level sufficiently to reduce PTH secretion. The effect of PTH on the kidneys occurs within minutes, whereas the effects of PTH on bone and (indirectly) on intestine take hours and days, respectively. An increase in serum phosphate acts in a way qualitatively similar to that of hypocalcemia to release PTH, increase excretion of phosphate in the proximal tubules, and decrease intestinal phosphate absorption. These events are mediated predominantly by the decrease in serum calcium that accompanies a rise in phosphate concentration. In addition, phosphate may inhibit 25-(OH)D-la-hydroxylase. 

Comparative studies Sodium phosphate versus polyethylene glycol In a randomized, open study of renal failure after administration of oral sodium phosphate solutions or solutions containing polyethylene glycol for bowel cleansing before colonic endoscopy, 93 patients with normal renal function were allocated to oral sodium phosphate (two 45-ml doses of Fleets Phos-phoSoda separated by 12 hours) or polyethylene glycol (4 liters of Colyte) combined with adequate hydration [85 ]. Renal function was assessed 1 week before, immediately before, and 1 week after colonoscopy. No subject had acute renal failure after either formulation. However, oral sodium phosphate was associated with significant rises in serum phosphate and... 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Other enzymes are also useful indices of liver pathology. Serum alkaline phosphatase is often a useful indicator of liver and bone disease. The alkaline phosphatases are a diverse group of enzymes that catalyze reactions in which a phosphate is removed from a phosphate ester, especially at an alkaline pH. Physicians don t care about this. They do care that serum alkaline phosphatase levels often rise with bone breakdown (as in tumor infiltration) and in liver disease, especially where tliere is obstruction of the bile duct. Acid phosphatase is particularly rich in the prostate. A rise in its serum levels provides a test as to the presence of prostate carcinoma. This test has largely been replaced by assay for Prostate Specific Antigen (PSA), a serine protease that is elevated in prostatic carcinoma. 

About 40% of serum calcium is protein bound, with most of it 80%) being bound to albumin. Generally, one or two calcium ions are associated with serum albumin. Albumin serves as a calcium buffer. Jt can bind more calcium ions when excessive concentrations of calcium appear in the bloodstream. About 13% of the calcium in scrum is weakly complexed with phosphate, citrate, and sulfate. About half (47%) of serum calcium occurs as the free calcium ion. The level of free scrum Ca is maintained within narrow limits, 1.0 to 1.25 mM (40 to 50 pg/mJ). The normal concentration of total serum calcium (bound plus free) is 85 to 105 pg/ml. Conditions in which the level of free serum calcium fails below and rises above the normal range are called hypocalcemia and hypercalcemia, respectively. The term ionized calcium is often used to refer to the concentrations of free calcium. This term is not scientifically accurate, because all of the calcium in the body is ionized. Calcium does not engage in the formation of covalent bonds (Cotton and Wilkinson, 1966). 

Since chronic renal insufficiency is frequently complicated by rises in serum potassium, phosphate, and magnesium, parenteral nutrition solutions used to treat malnourished patients with chronic renal insufficiency are usually prepared with little supplementation of these cations. Four patients with chronic renal insufficiency developed significant hypophosphatemia 3-5 days after starting parenteral nutrition. Other electrolyte abnormalities included hypomagnesaemia (n = 1) and hypokalemia (n — 3) (50). Hypophosphatemia may be the most significant of the electroljde risks in this clinical setting, and the electrolytes of such patients should be monitored closely when nutritional support is begun. 

The acute renal failure is typical for acute tubular necrosis and is characterized by a urine sediment with granular pigmented casts, and benzidine positive urine often in the absence of significant hematuria. With rhabdomyolytic acute tubular necrosis the urinary sodium concentration and fractional excretion of sodium are not always increased as in classic acute tubular necrosis [99]. One half to two-thirds of patients have ohguria, which may last from hours to many weeks. During this phase of the acute renal failure, there is a very rapid rise in the serum creatinine (often > 2.0 mg/ dl/ day), and profound increases in the serum levels of a variety of solutes normally foimd in muscle or produced from muscle derived precursors. Thus, fhe levels of potassium, phosphate, and uric acid all rise dra-... 

Since ATP normally inhibits 5 -nucleotidase and inorganic phosphate inhibits AMP deaminase, these changes would be expected to stimulate the catabolism of AMP to inosine. This hypothesis would most readily account for the rapid rise in serum urate concentration, the increased urinary excretion of inosine, oxypurines and uric acid, and the lack of an increase in intracellular PP-ribose-P levels following fructose infusion. 

The amount of calcium excreted in the urine is related to skeletal size, the acid-base regulation of the body, and the dietary protein intake. Urinary excretion of calcium rises when dietary protein is increased and falls when dietary protein is decreased, it appears that calcium losses can be substantial when protein intake is high hence, if this type of diet is continued for a prolonged period, it could result in a considerable loss of body calcium and even osteoporosis. FHow-ever, studies show that a high protein intake from a high meat diet has little effect on calcium excretion, possibly because of the high phosphate intake with the meat diet. A recent study suggests that increased phosphorus intakes reduce urinary excretion of calcium and lower serum calcium levels. 

EXCRETION OF PHOSPHORUS. The kidneys provide the main excretory mechanization for regulation of the serum phosphorus level. All of the plasma inorganic phosphate is filtered through the renal glomeruli, if the serum phosphorus level falls, the renal tubules return more phosphorus to the blood if the serum phosphorus level rises, the renal tubules excrete more. Also, when the diet lacks sufficient phosphorus, the renal tubules conserve phosphorus by returning it to the blood. On an average diet, an adult excretes from 0.6 to 1.0 g of phosphorus every 24 hours. 

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