Urine phosphates

The observed calcium/phosphate ratio of 4.5 at the intercept of the calcium and phosphate retention curves that should minimize the sum of the urine calcium plus urine phosphate losses was difficult to believe in view of both the known Ca/P ratio of bone and the amounts we were adding to these solutions. This disparity between the optimal ratio determined experimentally and what we had assumed this ratio should be on the basis of known body composition is partially reconciled by the experiment of Sutton and Barltrop. They fed preterm infants stable Ca46 and observed that up to 20% of the isotope absorbed was subsequently excreted in the stool. Our infants also were undoubtedly having unmeasured calcium losses from the bile, pancreatic juice and succus entericus secreted into their intestine... 

Our data from premature infants indicate that if both the urine calcium and the urine phosphate are between 2 and 10 mg/dl, the ratio of these elements in the alimentation solution is appropriate. 

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). 

Fig. 1, EflFect of 2.5 ml of commercial parathyroid extract (250 USP units) on urine phosphate excretion and the ratio of phosphorus to creatinine (P/Cr) in 20 subjects (mean values SE). Reproduced by permission of Clinical Science.

Howard et al. (Hll, H12), who suggested that the rise in plasma phosphate produced by intravenous calcium was due to parathyroid suppression, and that this rise was smaller than normal in hyperparathyroidism. It has since been shown that the effect of intravenous calcium on plasma phosphate is not a measure of parathyroid activity (N5), and this may explain why calcium infusions have tended to fall into disfavor. The fall in urine phosphate which follows calcium infusion does, however, indicate parathyroid suppression (K5, N5). Table 5 shows the effect of a standard calcium infusion on the urinary phosphate/creatinine ratio... 

D2. Davies, B. M. A., Gordon, A. H., and Mussett, M. V., A mouse urine phosphate assay for parathyroid hormone with certain applications. J. Physiol. (London) 180, 79-95 (1955). 

Phosphate makes a major contribution to the buffering of urine. Phosphates are derived from the products of metabolism and, on a typical western diet, 30 millimoles of phosphate, mainly dihydrogen phosphate, is excreted in the urine in 24 hours. 

In humans, thiamine is both actively and passively absorbed to a limited level in the intestines, is transported as the free vitamin, is then taken up in actively metabolizing tissues, and is converted to the phosphate esters via ubiquitous thiamine kinases. During thiamine deficiency all tissues stores are readily mobilhed. Because depletion of thiamine levels in erythrocytes parallels that of other tissues, erythrocyte thiamine levels ate used to quantitate severity of the deficiency. As deficiency progresses, thiamine becomes indetectable in the urine, the primary excretory route for this vitamin and its metaboHtes. Six major metaboHtes, of more than 20 total, have been characterized from human urine, including thiamine fragments (7,8), and the corresponding carboxyHc acids (1,37,38). 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

For a century after its discovery the only source of phosphorus was urine. The present process of heating phosphate rock with sand and coke was proposed by E. Aubertin and L. Boblique in 1867 and improved by J. B. Readman who introduced the use of an electric furnace. The reactions occurring are still not fully understood, but the overall process can be represented by the idealized equation ... 

Four batches of urokinase, obtained in this manner from 202 liters of urine, is pooled, amounting to 23.5 grams. The combined urokinase is suspended in 750 ml of 0.1 M phosphate-saline buffer at pH 6.2, stirred to dissolve the urokinase and centrifuged to remove the Celite. The residue is extracted two more times with 500 ml portions of 0.1 M phosphate-saline buffer. The combined extracts are filtered and labelled Extract 1. The residue is extracted three more times with 600 ml portions of buffer, the combined extracts are filtered and labelled Extract 2. 

The presence of sparingly soluble components in human urine, such as calcium oxalate, calcium phosphate, magnesium ammonium phosphate, uric acid and l-cystine. Kidney stones are composed mainly of these compounds. 

PTH is the most important regulator of bone remodelling and calcium homeostasis. PTH is an 84-amino acid polypeptide and is secreted by the parathyroid glands in response to reductions in blood levels of ionised calcium. The primary physiological effect of PTH is to increase serum calcium. To this aim, PTH acts on the kidney to decrease urine calcium, increase mine phosphate, and increase the conversion of 25-OH-vitamin D to l,25-(OH)2-vitamin D. PTH acts on bone acutely to increase bone resorption and thus release skeletal calcium into the circulation. However, due to the coupling of bone resorption and bone formation, the longer-term effect of increased PTH secretion is to increase both bone resorption and bone formation. 

Exposure Levels in Humans. Methyl parathion has been detected in serum and tissue shortly after acute exposure (EPA 1978e Ware et al. 1975). It is rapidly metabolized and does not persist in serum and tissues for long (Braeckman et al. 1983). Two metabolites of methyl parathion, 4-nitrophenol and dimethyl phosphate, can be detected in urine and tissues for up to 2 days following exposure (Morgan et al. 1977). These compounds are specific for methyl parathion when there is a history of exposure. 

A recent method to screen the urine for alkyl phosphates as an indicator of exposure to organophosphate insecticides shows that the method can be used to determine environmental exposure to a specific organophosphate pesticide. The method was found to be sensitive, identifying low levels of exposure to insecticides in the environment by quantitation of urinary phosphates (Davies and Peterson 1997). The test is limited in that it is only useful for assessing recent exposure, due to the short half-life of the organophosphate pesticides. 

Davies JE, Peterson JC. 1997. Surveillance of occupational, accidental, and incidental exposure to organophosphate pesticides using urine alkyl phosphate and phenolic metabolite measurements. Aim NY Acad Sci 837 257-268. 

Of all the elements, phosphorus is the only one that was first isolated from a human source. The element was extracted from human urine in 1669 using an unsavory process After a sample of urine was allowed to stand for several days, the putrefied liquid was boiled until only a paste remained. Further heating of the paste at high temperature produced a gas that condensed to a waxy white solid when the vapor was bubbled into water. It wasn t until 1779 that phosphorus was discovered in mineral form, as a component of phosphate minerals. 

Babson proposed a-naphthyl phosphate as an essentially specific substrate for the activity of prostatic acid phosphatase in serum (104). However Marshall, Price, and Amador found that this substrate is not specific for the prostatic enzyme because urine of human females contain 50 times more acid a-naphthyl phosphatase than male serum and 50% as much activity as male urine. Platelets have significant activity and the serum activity can increase to abnormal values following clotting. These workers also observed elevated activities in females with skeletal metastases of the breast. In 50 hospitalized male patients who had no evidence of prostatic cancer and 25 hospitalized female patients, the incidence of false positive results was 12%, a magnitude sufficient to preclude meaningful clinical interpretation (105). 

---