Phosphate clearance

PTH has a dual effect on bone cells, depending on the temporal mode of administration given intermittently, PTH stimulates osteoblast activity and leads to substantial increases in bone density. In contrast, when given (or secreted) continuously, PTH stimulates osteoclast-mediated bone resorption and suppresses osteoblast activity. Further to its direct effects on bone cells, PTH also enhances renal calcium re-absorption and phosphate clearance, as well as renal synthesis of 1,25-dihydroxy vitamin D. Both PTH and 1,25-dihydroxyvitamin D act synergistically on bone to increase serum calcium levels and are closely involved in the regulation of the calcium/phosphate balance. The anabolic effects of PTH on osteoblasts are probably both direct and indirect via growth factors such as IGF-1 and TGF 3. The multiple signal transduction... 

One of the reasons for suspecting that variations in parathyroid functioning are great is the fact that experimental animals have striking individual sensitivity to administered hormone. This fact has been noted particularly in dogs which have been used for assay animals. Also, in one study involving humans it was found that four normal individuals had their phosphate clearance increased 60 per cent, 190 per cent, 150 per cent, and 110 per cent, respectively, when 200 units of the hormone was administered intravenously, while two individu-... 

Fio. 12. Scheme of calcium and phosphorus homeostasis in progressive renal disease — , increases decreases GFR, glomerular filtration rate P, serum phosphorus Ca2+, serum ionized calcium Ca, calcium 1,25-DHCC, 1,25-dihydroxy cholecalciferol PTH, serum parathyroid hormone Cp, phosphate clearance. 

Parathyroidectomy is followed by a fall in urine phosphate excretion and a consequential rise in plasma inorganic phosphate concentration until a new equilibrium is established (Tl). In clinical hypoparathyroidism, plasma inorganic phosphate may be as high as 10 mg/100 ml, but the amount of phosphorus excreted in the urine by such patients really depends upon dietary intake. In these cases, therefore, phosphate clearance is usually low and is always low when considered in relation to the plasma phosphate concentration (K4, N6, Nil). 

Several phosphate excretion tests have been devised to assist in the assessment of parathyroid activity from the study of the renal excretion of phosphorus. All workers are agreed that plasma phosphate tends to be high and phosphate clearance low in hypoparathyroidism and that... 

A. The measurement of phosphate clearance from a timed sample of urine and a simultaneous blood sample (K6). The normal range is reported as 6.3-15.5 ml/min. Higher and lower values were found in a series of cases of hyper- and hypoparathyroidism, respectively. The authors have made no attempt to correct their clearances to take into account the effect of plasma phosphate concentration upon phosphate clearance (see below). 

The determination of phosphate clearance is a very simple procedure whieh involves only phosphate estimations. However, it is almost certainly too crude to be useful. In a recent series (R5), it yielded very poor discrimination between hyperparathyroid and euparathyroid subjects (Fig. 11). It would probably be improved by the introduction of a correction for plasma level, but, even so, precision requires catheterization which is undesirable in a routine test. 

Malignancy. Hypercalcemia may occur in association with cancer without bone metastases (P4), and cases have been reported with a raised phosphate clearance (T7). This type of hypercalcemia does not usually respond to cortisone, but the hypercalcemia of myelomatosis may do so. 

Vitamin D contributes to the calcemic action of the parathyroid hormone (C2, N14). Deficiency of vitamin D therefore results in a fall in ionic calcium concentration which stimulates the parathyroids. Parathyroid hypertrophy is seen in vitamin D-deficient animals (C3, H7, S7) and man (PI) and can be prevented by exposure to ultraviolet light (H7). A low plasma phosphorus concentration and high Cp/Ca are characteristic of osteomalacia and rickets, and the FEl is of the same order as that in parathyroid tumor (Nil) (Fig. 10). However, this high phosphate clearance, unlike that of parathyroid tumor, can be reduced to a normal or subnormal value by intravenous infusion of calcium (N5). 

ML McGeown, M. G., Normal standards of renal phosphate clearance and observations on calciilus patients. Clin. Sd. 16, 2 7-3(n (1956). 

This is why the determination of phosphate excretion in daily urine is clinically not very meaningful and should be supplemented by measurements of (1) phosphate clearance, (2) fractional tubular phosphate reabsorption, and (3) maximum tubular phosphate reabsorption. 

The ratio of the phosphate clearance (CJ to the creatinine clearance (Ccr) gives an indication of the proportion of phosphate filtered at the glomerulus which has been reabsorbed by the renal tubules (a process in which parathyroid hormone is involved). In order to allow for fluctuations in the level of serum phosphate, the phosphate excretion index (PEI) was devised and this is given by the formula ... 

Saline laxatives containing magnesium, potassium, or phosphates should be used cautiously in persons with reduced kidney function. Monitor appropriate serum electrolyte concentrations in patients with unstable renal function evidenced by changing serum creatinine or creatinine clearance. 

The isotope tracer method for estimating the total muscle mass of an organism by determining the amount of creatinine clearance. The method relies on the fact that muscle creatine phosphate is converted to creatine, and the latter is metabolized into creatinine. 

Opiates can effect serum levels of enzymes and other substances whose homeostatic control depends on clearance through the liver (F8, G12, M15, N4, S19). In one reported case, the aspartate aminotransferase was within normal limits before the administration of codeine, but within 2 hours after the drug, the enzyme activity had risen to two times the normal value by 8 hours to eight times the normal activity, and within 24 hours it had returned to normal (F8). Increases in transaminase to levels 5-85 times the control value have been reported in 6 of 16 patients with disease of the biliary tree following the administration of codeine phosphate (2 grains) (B7, F8). Gross has shown that morphine, codeine, or mepheridine administration produce elevations of serum amylase or lipase (G12). These elevations have been attributed to constriction of the sphincter of Oddi and increased intraductal pressure on the pancreatic duct (G12, N4). 

These salts should always be given with substantial amounts of water otherwise the patient may be purged at the expense of body water, resulting in dehydration. Sodium-containing laxatives should not be used in patients with congestive heart failure, since the patient may absorb excessive sodium. Similarly, in cases of renal failure, magnesium or phosphate-containing products should not be used, since the loss of a renal clearance of these ions may result in cumulative toxic levels despite their minimal absorption. 

Mechanism of Action A synthetic polypeptide hormone that acts on bone to mobilize calcium also acts on kidney to reduce calcium clearance, increase phosphate excretion. Therapeutic Effect Promotes an increased rate of release of calcium from bone into blood, stimulates new bone formation. 

No particular work-up is required before starting a child on Buspirone. If liver disease is suspected, a serum level of alkaline phosphate can be obtained because decreases in clearance are directly correlated with increases in alkaline phosphate (Gammans et ah, 1986). 

J. Rossi, A.E. Jung, D. Ritchie, J.W. Lindsey, A.E. Nordholm, Tissue distribution, metabolism, and clearance of the convulsant trimethylol propane phosphate in rats, Drug Metabolism and Disposal, 26, 1058-1062, 1998. 

Riboflavin and riboflavin phosphate that are not bound to plasma proteins are filtered at the glomerulus the phosphate is generally dephosphorylated in the bladder. Renal tubular reabsorption of riboflavin is saturated at normal plasma concentrations, and there is also active tubular secretion of the vitamin, so that urinary clearance of riboflavin can be two- to three-fold greater than the glomerular filtration rate. 

Because the erythrocyte volume increases under the influence of erythropoietin, the clearance achieved by the dialyser can fall, with a consequent increase in creatinine, potassium, and phosphate (101). However, earher fears that the renal function of predialysis patients receiving epoetin might deteriorate prematurely have not been realized (65). 

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