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Phosphorus depletion in children on long-term total parenteral nutrition.

The retention of nitrogen, calcium and phosphorus was studied in nine infants on total parenteral nutrition. The amounts of calcium, nitrogen and phosphorus were varied singly or simultaneously. The results demonstrate close interrelationships in the retention of these three elements. Not only the absolute amount of phosphorus perfused daily but also the amounts of nitrogen and/or calcium perfused simultaneously account for the phosphorus depletion that may lead to severe hypophosphatemia. The decrease in serum phosphorus concentration with a simultaneous fall of urinary phosphorus excretion to undetectable levels and a rise in urinary calcium output to 10 mg/kg/24 hours or more are warning symptoms of phosphorus depletion. Such a complication was observed in our first seven children on total parenteral nutrition. Phosphorus depletion can be prevented by using the following amounts of these elements in the perfusate: per 100 Kcal/kg/24 hours, 400 mg/kg/24 hours of nitrogen, 35 mg/kg/24 hours of calcium and 40 mg/kg/24 hours of phosphorus. With such a technique no phosphorus depletion was observed in any of the 63 subsequent patients whom we treated with total parenteral nutrition for periods varying from 20 days to 9 months.

Amino Acids

Renal response to phosphorus deprivation: effect of the parathyroids and bicarbonate.

Plasma inorganic phosphate (Pi) and Pi reabsorption were compared in intact and chronically thyroparathyroidectomized (TPTX) rats stabilized on a high or low-phosphorus diet after volume expansion with equivalent sodium bicarbonate or sodium chloride. Phosphate infusion after sodium chloride-loading resulted in greater hyperphosphatemia and diminished phosphaturia in TPTX rats than intact high-phosphorus rats. After sodium bicarbonate-loading, however, there was no difference between intact and TPTX high-phosphorus animals because bicarbonate inhibited Pi reabsorption extensively in both. In contrast, phosphate infusion after sodium chloride-loading in phosphorus-deprived rats elicited greater degrees of hyperphosphatemia and increased Pi reabsorption, irrespective of the presence or absence of the parathyroids. Sodium bicarbonate-loading inhibited Pi reabsorption significantly less in phosphorus-deprived rats than in high-phosphorus animals. Paradoxically, this inhibitory effect of bicarbonate in phosphorus depletion was greater in TPTX rats than in intact animals. Therefore, the presence of the parathyroids did not interfere with Pi reabsorption during phosphate infusion in sodium bicarbonate-loaded phosphorus-deprived rats. Sodium bicarbonate-loading interfered with Pi reabsorption most prominently in phosphorus-deprived rats when the parathyroids were absent.

Animals

Blood phosphorus levels of laying hens at various time intervals after dosing with phosphoric acid.

Two experiments were conducted to study the pattern of change in serum inorganic phosphorus level in laying hens fed a diet containing 0.30% total phosphorus after dosing with a known amount of phosphorus. Serum phosphorus level of undosed hens was 2.5 mg/100 ml at oviposition in both experiments. After dosing with 100 mg of phosphorus in 10 ml of a phosphoric acid solution, serum phosphorus level increased sharply and reached a peak of about 7.0 mg/100 ml between 30 and 60 minutes in experiment 2. After the peak the elevated level of serum phosphorus decreased logarithmically until 5 to 6 hours after dosing and eventually decreased to 2.5 mg/100 ml which was the serum phosphorus level of undosed hens in experiment 1. The half-life of the elevated portion of serum phosphorus due to the dosing was about 100 minutes.

Animals

Influence of dietary phosphorus on renal phosphate reabsorption in the parathyroidectomized rat.

Inorganic phosphate (Pi) reabsorption was studied during Pi infusion, after acute or chronic thyroparathyroidectomy (TPTX), in rats stabilized on a high-phosphorus (1% P) or a low-phosphorus (0.02% P) diet. After acute TPTX, there were no consistent differences in Pi reabsorption between the high- and low-phosphorus dietary groups. After chronic TPTX, the rats stabilized on the low-phosphorus diet exhibited nearly complete Pi reabsorption at every plasma Pi level, while the animals receiving the high-phosphorus diet manifested a marked phosphaturic response to Pi infusion. In addition, Pi reabsorption was significantly increased in the chronic TPTX low-phosphorus rats which achieved the highest filtered Pi loads, while their urine remained essentially phosphate-free. Dietary phosphorus-dependent alterations in Pi reabsorption may play a significant role in establishing the rate of Pi excretion per nephron under certain circumstances and should be considered in the interpretation of studies investigating renal Pi handling. The ability of phosphorus-depleted animals to maintain a phosphate-free urine during Pi loading would favor the rapid repletion of body phosphorus stores.

Absorption

Renal resistance to parathyroid hormone during phosphorus deprivation.

Because previous studies have demonstrated that renal inorganic phosphate reabsorption is enhanced in rats after dietary phosphorus deprivation, we studied the effects of parathyroid hormone (PTH) upon inorganic phosphate reabsorption in acutely thyroparathyroidectomized rats stabilized on a low phosphorus diet to determine if the phosphaturic response to PTH is impaired during phosphorous depletion. Acutely thyroparathyroidectomized phosphorus-deprived rats responded only minimally to PTH, whereas similarly prepared animals stabilized on a high phosphorus diet exhibited a large phosphaturic response. Base-line urinary cyclic AMP values and PTH-induced increases in cyclic AMP excretion were similar in both groups. In other experiments, dibutyryl cyclic AMP elicited a greatly diminished phosphaturic response in phosphorus-deprived rats, as compared to their high phosphorus counterparts. These results indicate that the renal phosphaturic responses to PTH and cyclic AMP are impaired during dietary phosphorus deprivation. The impaired phosphaturia would contribute to phosphorus conservation and to the replenishment of inorganic phosphate stores after phosphorus depletion.

Animals

[Effect of long-term administration of thyroxine on the content of nucleic acids and certain indicators of phosphorus metabolism in the liver in experimental thyrotoxicosis].

In the liver of albino rats with experimental thyrotoxicosis a study was made of nucleic acids and some indices of phosphorus metabolism: total and inorganic phosphorus, total and acid-soluble phosphorus, phosphorus of RNA, DNA and phosphoproteins. A significant elevation of the RNA and DNA content was noted 1 1/2 months from the beginning of the experiment. An increase of the concentration of nucleic acid phosphorus and a simultaneous reduction of the content of phosphorus of phosphoproteins and inorganic phosphorus was noted in the phosphorus metabolism indices under study. The content of total and acid-soluble phosphorus displayed no significant change. The data obtained indicated that, along with increased catabolism in thyrotoxicosis there occurred rather intensive synthesis, without reaching the normal level, however.

Animals

Identification of organic phosphorus covalently bound to collagen and non-collagenous proteins of chicken-bone matrix. The presence of O-phosphoserine and O-phosphothreonine in non-collagenous proteins, and their absence from phosporylated collagen.

Non-collagenous phosphoproteins, almost all of which can be extracted in EDTA at neutral pH in the presence of proteinase inhibitors, are identified in the matrix of chicken bone, and are therefore not covalently bound to collagen. Similarly, all the peptides containing gamma-carboxyglutamic acid are present in the EDTA extract and none in the insoluble residue, confirming that none is covalently linked to chicken bone collagen. However, organic phosphorus is also found to be present in chicken bone collagen, principally in the alpha2-chains. Of the total protein-bound organic phosphorus present in chicken bone matrix, approx. 80% is associated with the non-collagenous proteins and 20% with collagen. The soluble non-collagenous proteins contain both O-phosphoserine and O-phosphothreonine and these account for essentially of their organic phosphorus content. In contrast, collagen contains neither O-phosphoserine nor O-phosphothreonine. Indeed, no phosphorylated hydroxy amino acid, phosphoamidated amino acid or phosphorylated sugar could be identified in purified components of collagen, which contain approximately four to five atoms of organic phosphorus per molecule of collagen. Peptides containing organic phosphorus were isolated from partial acid hydrolysates and enzymic digests of purified collagen components, which contain an as-yet-unidentified cationic amino acid. These data, the very high concentrations of glutamic acid in the phosphorylated peptides, and the pH-stability of the organic phosphorus moiety in intact collagen chains strongly suggest that at least part of the organic phosphorus in collagen is present as phosphorylated glutamic acid. This would indicate that the two major chemically different protein fractions in chicken bone matrix that contain organic phosphorus may represent two distinct metabolic pools of organic phosphorus under separate biological control.

1-Carboxyglutamic Acid

Effect of long-term lithium administration on renal phosphorus handling.

Renal phosphorus handling was evaluated in 12 lithium carbonate-treated psychiatric patients. Serum phosphorus was normal and serum lithium values were within the therapeutic range in all subjects. Serum calcium concentrations measured in 6 of the patients were found to be within the normal range; in the same patients serum parathyroid hormone levels were normal in 4 and slightly elevated in 2. Phosphorus clearance (14 +/- 3 [se] ml/min) and tubular reabsorption of phosphorus (88 +/- 2%) during oral sodium bicarbonate loading were not significantly different from those in 10 healthy control subjects. In a subgroup of 5 patients and 5 control subjects, phosphorus excretion did not increase after bicarbonate loading. In these subjects, phosphorus excretion rates after bicarbonate loading were not different. Although experimental studies suggest that lithium inhibits renal cortical adenylate cyclase stimulation by parathyroid hormone, our data did not indicate any striking effect of long-term lithium administration on serum calcium and serum phosphorus or on renal phosphorus handling.

Adenylyl Cyclase Inhibitors

Metabolism in vitro of 25-hydroxycholecalciferol in chicks fed on phosphorus-deficient diets.

1. Three groups of 10-days-old chicks were fed on one of three diets having phosphorus contents of 0.08 mol/kg, 0.14 mol/kg or 0.21 mol/kg. Ten days later duodenal calcium absorption by the ligated loop technique in vivo, and plasma calcium and phosphorus concentrations, were measured. In addition the metabolism in vitro of 25-hydroxycholecalciferol [25-(OH)D3] by kidney homogenates was studied. 2. In the low phosphorus group (0.08 mol/kg) calcium absorption and the activity of 25-(OH)D3-1-hydroxylase were significantly higher than those of the high phosphorus group (0.21 mol/kg). However, in the medium phosphorus group (0.14 mol/kg), calcium absorption was significantly higher although the activity of 25-(OH)D3-1-hydroxylase was not significantly higher when compared with the high phosphorus group (0.21 mol/kg). 3. It is concluded that in phosphorus deprivation, unlike in calcium deprivation, a diet very low in phosphorus is required to stimulate the renal 25-(OH)D3-1-hydroxylase activity.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Calcium and phosphorus requirements of the laying hen.

Three experiments were conducted; the first studied the influence of pre-laying dietary calcium levels on subsequent hen performance, while in the second and third the influence of various levels of dietary calcium and phosphorus on performance, egg shell quality and calcium and phosphorus retention were investigated. Pre-dietary calcium levels (0.5 and 1.5%) resulted in a significant strain X diet interaction for weight gain up to commencement of lay but did not influence production, feed intake, egg size or sheel quality. Dietary calcium levels varying from 2.5 to 4.0% did not significantly alter the avove parameters during a 140 day laying test. Compared to a non-pelleted control diet, steam pelleting resulted in a significant enhancement in phosphorus availability is judged by higher levels of performance. Percent calcium retention varied with the level of dietary calcium and there was an indication that level of dietary phosphorus influenced calcium retention. Lower levels of dietary phosphorus resulted in egg shells with slightly lower deformation values. Regardless of dietary phosphorus, retention values were quite low. Changing the level of dietary calcium and phosphorus had little or no effect on the retention of phosphorus thus suggesting a relatively constant and low requirement for this nutrient.

Animal Feed

The dissipation of phosphorus in sewage and sewage effluents.

Of the 41 kt of phosphorus reaching the sewage works in England and Wales 15 kt is removed in sewage sludge and the remainder is disposed of to rivers. 60% of the sewage sludge is now used as fertilizer and this proportion will no doubt increase in the future. The total use of sewage sludge, however, represents only about 5% of the current annual usage of artificial phosphorus fertilizer. At present there is no general economic incentive to make better use of the phosphorus in effluents. Phosphorus removal is expensive--about 2--3 pence/m3. If all the sewage effluents in England and Wales were to be so treated the cost would be about 100--150 million pounds annually, that is about 50% of the present costs of sewage treatment. In certain cases, but rarely in the UK, phosphate is removed, not to conserve phosphorus but to minimize the problems it creates in the environment. The phosphorus removed has little value as fertilizer. Alternative methods of using the phosphorus in effluents by the production and harvesting of crops of algae or aquatic plants have so far proved uneconomic. However, these methods need to be reviewed periodically as they may in the future become economically more attractive, especially in warmer climates where plant growth can be maintained throughout the year.

Adult

Calcium and phosphorus deficiency in rats: effects on PTH and 1,25-dihydroxyvitamin D3.

Weanling male Holtzman rats were fed calcium.deficient, phosphorus-deficient, or control diets for 8 wk. Parathyroid hormone (PTH) was measured by radioimmunoassay, and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) by a competitive binding assay. Rats fed the calcium-deficient diet (0.01% calcium, 0.6% phosphorus) became mildly hypocalcemic after 6 days. Serum calcium levels reached 5.5 +/- 0.4 mg/dl (mean +/- SD) in 5 wk (control 10.3 +/- 0.4 mg/dl). PTH increased from 285 +/- 112 to 3658 +/- 428 pg/ml within 6 wk. Maximum serum levels of 1,25(OH)2D3 (111.8 +/- 17.3 vs. control 11.4 +/- 3.8 ng/dl) were reached at 3 wk and thereafter declined to 44.6 +/- 14.0 ng/dl. In rats fed the phosphorus-deficient diet (0.6% calcium, 0.04% phosphorus), serum phosphorus fell within 24 h from 9.1 +/- 0.6 to 3.2 +/- 0.1 mg/dl, recovered to 5.6 +/- 0.4 mg/dl for 2-3 days, and then declined again. Serum calcium reached a maximum of 14.4 +/- 0.4 mg/dl at day 2 (control 10.8 +/- 0.5 mg/dl) and then slowly declined. PTH decreased within 24 h from 243 +/- 59 to 36 +/- 0 pg/ml in phosphorus-depleted rats. Serum levels of 1,25(OH)2D3 increased within 24 h and remained elevated after 6 wk of phosphorus deprivation (61.2 +/- 11.7 ng/dl vs. control 18.3 +/- 0.4 ng/dl).

Animals

Assessment of the quantity of biologically available phosphorus in yeast RNA and single-cell protein.

Two assays were conducted with chicks fed a phosphorus-deficient crystalline amino acid diet from day 8 to 17 posthatching to evaluate the phosphorus availability of purified torula yeast RNA and single-cell protein (Torula yeast). Tibia bone ash of the chicks was the criterion used in both assays, and regression analysis was used to evaluate bone ash as a function of phosphorus intake. A standard curve was established by feeding graded levels of KH2PO4 in each assay. Weight gain, tibia weight and tibia ash all responded to phosphorus supplementation whether provided by KH2PO4, RNA or single-cell protein. Weight of tibia ash provided the best linear fit when evaluated as a function of phosphorus intake. Availability in both assays estimated using the slope-ratio technique wherein milligrams of available phosphorus per gram of RNA or single-cell protein was calculated. In assay 1 the available phosphorus in RNA was found to be 93.2 mg/. In assay 2 the available phorphorus in single-cell protein was found to be 14.1 mg./g.

Animal Feed

Relative phosphorus requirements of three strains of White Leghorn cockerels.

Three strains of White Leghorn Cockerels were fed a degerminated corn meal diet supplemented with graded levels of phosphorus. The basal diet which contained .30% phosphorus and .21% calcium was adjusted to contain added phosphorus levels of 0, .05, .10, or .15%, with calcium levels of .49, .47, .57 and .61%, respectively. At the end of a 21-day trial period, birds were group weighed by replicate, and four birds from each replicate sacrificed for bone ash determinations. The experiment was repeated one time. Maximum body weights of Babcock B-300 and Hyline W-36 chicks was attained at the .10% supplemental phosphorus level; whereas Kimber K-137 chick body weight data indicated a response beyond this point to the .15% level. Bone ash data indicated that there may be a difference in phosphorus requirement and/or utilization among the three strains. There was no significant response beyond the .10% supplemental phosphorus level when tibia ash values of the B-300 and W-36 chicks were analyzed. A significant response in ash values was noted, however, to the .15% supplemental phosphorus level with K-137 chicks.

Animals

[Idiopathic hypercalciuria: effects of acute phosphorus deficiency (author's transl)].

Eleven patients with kidney stone disease and idiopathic hypercalciuria (urinary calcium above 4 mg/kg/j), without phosphorus renal leak and 6 control subjects have been put for 3 days on a diet containing 1 g calcium and 1 phosphorus daily (period A), and then for 4 days on a diet containing 1 g calcium, 450 mg phosphorus and 3 g aluminium hydroxyde daily (period B). During period A, no significant difference in blood calcium, phosphorus and magnesium, not in phosphaturia, rate of phosphorus reabsorption (RPR) and ratio maximum RPR/creatinine clearance was found between the two groups. After 2 days on a low phosphate diet (period B) the blood phosphorus decreased significantly in the hypercalciuric patients but not in the control subjects, thus revealing among the forme a latent abnormality in the retention of phosphates. This abnormality could play an important role in the pathogenesis of hypercalciuria.

Adult

Effect of hydrochlorothiazide on phosphorus during treatment with diphosphonate.

The effects of probenecid and hydrochlorothiazide on renal handling of phosphorus during hyperphosphatemia induced by diphosphonate (ethane-1-hydroxy-1, 1-diphosphonate, EHDP) was studied. Measurements of calcium, phosphorus, and creatinine clearance were performed in 2 sessions on each of 3 consecutive days in 10 normal fasting volunteers during the morning hours from 8 A.M. to 12 noon. During 2 to 3 wk thereafter, each subject was treated with EHDP, 30 mg/kg/day. The second group of studies were performed in the same manner as the first except the EHDP administration was continued throughout. EHDP caused elevation of serum phosphorus in all cases. Probenecid did not affect urine phosphorus. Hydrochlorothiazide caused a transient phosphaturia of similar magnitude in the EHDP treated and untreated states. Creatinine clearance was not affected by any of the treatments and urine calcium was decreased by EHDP. It was concluded that hydrochlorothiazide inhibits tubular reabsorption of phosphorus but that it does not affect the mechanism whereby EHDP causes increased tubular reabsorption of phosphorus. Chronic administration of hydrochlorothiazide along with EHDP may inhibit hyperphosphatemia and may change the bone effects of EHDP.

Adult

Phosphorus, a key to life on the primitive Earth.

The phosphorus of the primitive Earth was present as phosphates. It is strongly probably that a portion of the phosphate was present as condensed phosphates. The primitive Earth was highly deficient in the total available phosphorus until a sufficient quantity of phosphorus weathered from the igneous rocks in which it was entrapped. Approximately three billion years were required for the seas to become saturated. Until this time passed the seas acted as a giant sink for phosphorus, diluting it to the extent that all forms of life were deprived of the vital nutrient. When the seas became saturated, the rate of turn over of the phosphorus increased rapidly. As the seas pulsated, they left the excess precipitate phosphorus as sedimentary rock in locally righ deposits on which life could thrive.

Apatites

The effect of fluoride on bone of rats fed diets deficient in calcium or phosphorus.

Four groups of weanling rats were fed for 2 weeks on a diet sufficient or insufficient in calcium and/or phosphorus. Each group was divided into four subgroups which were offered distilled water supplemented with 0, 50, 75, or 150 ppm fluoride. High levels of fluoride in drinking water inhibited weight gain. This inhibition was less in rats deficient in phosphorus than when normal-phosphorus diets were offered. At a low level, fluoride was without any effect on bone ash, thickness of femoral cortical bone, and mechanical strength, as measured by maximal load, ultimate stress to breaking, and limit of elasticity. Modulus of elasticity was decreased. At higher levels fluoride tended to decrease most of these parameters, except in rats deprived of both calcium and phosphorus. The effect of fluoride was modified by lack of dietary calcium and/or phosphorus and appeared to be weaker in rats deficient in these nutrients. Lack of dietary calcium and/or phosphorus decreased bone strength more than did fluoride content of water and of bone mineral. Concentration of bone ash and thickness of femoral cortical bone were closely correlated with parameters of mechanical strength.

Animals