Kidney phosphorus

Decreasing phosphorus reabsorption in the proximal tubules in the kidney... 

As kidney function continues to decline and the GFR falls less than 60 mL/minute/1.73 m2, phosphorus excretion continues to decrease and calcitriol production decreases, causing PTH levels to begin to rise significantly, leading to secondary hyperparathyroidism (sHPT). The excessive production of PTH leads to hyperplasia of the parathyroid glands, which decreases the sensitivity of the parathyroid glands to serum calcium levels and calcitriol feedback, further promoting sHPT. 

These adaptations are lost as renal failure progresses. [Ca] X [POJ calcium-phosphorus product. (From Joy MS, Kshirsagar A, Paparello J. Chronic kidney disease Progression-modifying therapies. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 834, with permission.)... 

Ca-P, calcium-phosphorus product CKD, chronic kidney disease PTH, parathyroid hormone. 

A study with a dog exposed to an occluded dermal dose of TOCP labeled with radioactive phosphorus provides limited evidence that organophosphate esters in hydraulic fluids may be widely distributed after dermal absorption (Hodge and Sterner 1943). Similar widespread distribution of radioactivity among tissues was observed in male cats after dermal exposure to [uniformly labeled 14C-phenyl]TOCP (Nomeir and Abou-Donia 1986). Tissues and fluids with the highest concentrations of radioactivity in these studies included the bile, gall bladder, urinary bladder, liver, kidney, and fat, thus suggesting that TOCP and metabolites are somewhat preferentially distributed to these tissues. 

Twenty-four hours after application of 2.094 g TOCP labeled with radioactive phosphorus to a 15x20 cm area of clipped and depilated abdominal skin, radioactivity was detected in the following tissues in a dog, listed in order of decreasing concentration (counts per gram of tissue) skin and facia at site of application, liver, omental fat, blood, kidney, lung, muscle (triceps femoris), spinal cord, heart, spleen = brain = sciatic nerve, and bone (femur) (Hodge and Sterner 1943). 

Sodium, potassium, magnesium, and phosphorus requirements are typically decreased in patients with kidney failure, whereas calcium requirements are increased (see Chaps. 76 and 78). 

Calcium-phosphorus balance is mediated through a complex interplay of hormones and their effects on bone, GI tract, kidney, and parathyroid gland. As kidney disease progresses, renal activation of vitamin D is impaired, which reduces gut absorption of calcium. Low blood calcium concentration stimulates secretion of parathyroid hormone (PTH). As renal function declines, serum calcium balance can be maintained only at the expense of increased bone resorption, ultimately resulting in renal osteodystrophy (ROD) (Fig. 76-7). 

Kidney Disease/Dialysis Outcomes Quality Initiative (K/DOQI) Guidelines for Calcium (C), Phosphorus (P), Calcium Phosphorus Product, and Intact Parathyroid Hormone... 

As can be seen from the results in Table V, fluoride levels in plasma, liver and kidney increased 3 to 8 times but there was no significant effect on the calcium or phosphorus content, although the kidney Ca level in fluoride treated rats was 40 higher than in the controls. Whereas the normal exposure to fluoride from air, food and water did not cause any increase in soft tissue levels, more than ten times the normal levels in soft tissues, including liver and kidney, were found in human fatalities due to fluoride poisoning (15). 

Finally we should briefly mention the purple acid phosphatases, which, unlike the alkaline phosphatases, are able to hydrolyse phosphate esters at acid pH values. Their purple colour is associated with a Tyr to Fe(III) charge transfer band. The mammalian purple acid phosphatase is a dinuclear Fe(II)-Fe(III) enzyme, whereas the dinuclear site in kidney bean purple acid phosphatase (Figure 12.13) has a Zn(II), Fe(III) centre with bridging hydroxide and Asp ligands. It is postulated that the iron centre has a terminal hydroxide ligand, whereas the zinc has an aqua ligand. We do not discuss the mechanism here, but it must be different from the alkaline phosphatase because the reaction proceeds with inversion of configuration at phosphorus. 

Vitamin D is converted in the liver and kidneys to 1,25-dihydroxyvitamin D, which is the hormone-active compounds. The principal physiological function is to maintain the serum calcium and phosphorus concentrations in a range that support cellular processes, neuromuscular function, and bone ossihcation [417], Only a few foods contain vitamin D in quantities that have an impact on the dietary intake hsh liver, hsh liver oils, fatty fish, and egg yolks. Thus, some countries practice fortihcation of certain foods with vitamin D, most often milk, margarine, and/or butter. 

Vitamin D3 is transported to liver where it undergoes a hydroxylation at C-25 into 1a,25-dihydroxyvitamin D3 (calcitriol) (Fig. 64). In the kidney, it undergoes further hydroxylations at different sites, depending on the serum Ca + concentration. The most biologically active metabolite of vitamin D3 is calcitriol, which plays important roles in the regulation of calcium and phosphorus metabolism. It is used for treating bone diseases, but is also involved in the cell proliferation and the inducement of cell differentiation [151]. 

Sevelamer For control of serum phosphorus in patients with chronic kidney disease and hemodialysis... 

Calcium and phosphate enter the body from the intestine. The average American diet provides 600-1000 mg of calcium per day, of which approximately 100-250 mg is absorbed. This figure represents net absorption, because both absorption (principally in the duodenum and upper jejunum) and secretion (principally in the ileum) occur. The amount of phosphorus in the American diet is about the same as that of calcium. However, the efficiency of absorption (principally in the jejunum) is greater, ranging from 70% to 90%, depending on intake. In the steady state, renal excretion of calcium and phosphate balances intestinal absorption. In general, over 98% of filtered calcium and 85% of filtered phosphate is reabsorbed by the kidney. The movement of calcium and phosphate across the intestinal and renal epithelia is closely regulated. Intrinsic disease of the intestine (eg, nontropical sprue) or kidney (eg, chronic renal failure) disrupts bone mineral homeostasis. 

Conversion of 7-dehydrocholesterol to vitamin D3 and metabolism of D3 to l,25(OH)2D3 and 24,25(OH)2D3. Control of the latter step is exerted primarily at the level of the kidney, where low serum phosphorus, low serum calcium, and high parathyroid hormone favor the production of l,25(OH)2D3, whereas fibroblast growth factor 23 inhibits its production. The inset shows the... 

Kirkbride (1987) described the estimation of diazinon in human omental tissue (fatty tissue) after a fatal poisoning. In this method, the tissue was pulverized and extracted with acetone. After extract concentration and purification by sweep co-distillation and Florisil fractionation, diazinon was measured by gas chromatography (GC) with nitrogen-phosphorus detection (NPD). After another fatal diazinon poisoning, diazinon was quantified by GC/electron capture detection (ECD) and GC/flame ionization detection (FID) by Poklis et al. (1980). The diazinon in human adipose, bile, blood, brain, stomach contents, kidney, and liver was recovered by macerating the sample with acetonitrile followed by the addition of aqueous sodium sulfate and extraction into hexane. Following an adsorption chromatography clean-up, the sample was analyzed. 

Trechsel, U., Bonjour, J. P., Fleisch, H. Influence of dietary calcium, phosphorus, and vitamin D on the conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxy-vitamin D3 by kidney tubules of diphosphonate-treated quails. Calc. Tiss. Res. 22, 461 (1977)... 

Magnesium. In the adult human, 50-70 T ol the magnesium is in the hones associated w ilh calcium and phosphorus. The rest is widely distributed in the soft tissues and body fluids. Most of the nonhone Mg 1, like K. is located in the intracellular lluid where it is the most abundant divalent cation. Magnesium ton is efficiently retained by the kidney when the plasma concentration of Mg falls in this respect it resembles Na. The functions of Na. K. Mg . and Ca- are interrelated so that a deficiency of Mg " affects the metabolism of the other three ions. 

The excretion of body phosphorus occurs via the kidney and intestinal tract, the distribution between these pathways varying with species. For example, relatively small amounts of phosphorus are endogenously excreted into the feces of rat, pig, and human, but in the bovine, perhaps 50% or more of the fecal phosphorus may be from endogenous sources. 

Vitamin D3 is a precursor of the hormone 1,25-dihy-droxyvitamin D3. Vitamin D3 is essential for normal calcium and phosphorus metabolism. It is formed from 7-dehydrocholesterol by ultraviolet photolysis in the skin. Insufficient exposure to sunlight and absence of vitamin D3 in the diet leads to rickets, a condition characterized by weak, malformed bones. Vitamin D3 is inactive, but it is converted into an active compound by two hydroxylation reactions that occur in different organs. The first hydroxylation occurs in the liver, which produces 25-hydroxyvita-min D3, abbreviated 25(OH)D3 the second hydroxylation occurs in the kidney and gives rise to the active product 1,25-dihydroxy vitamin D3 24,25 (OH)2D3 (fig. 24.13). The hydroxylation at position 1 that occurs in the kidney is stimulated by parathyroid hormone (PTH), which is secreted from the parathyroid gland in response to low circulating levels of calcium. In the presence of adequate calcium, 25(OH)D3 is converted into an inactive metabolite, 24,25 (OH)2D3. The active derivative of vitamin D3 is considered a hormone because it is transported from the kidneys to target cells, where it binds to nuclear receptors that are analogous to those of typical steroid hormones. l,25(OH)2D3 stimulates calcium transport by intestinal cells and increases calcium uptake by osteoblasts (precursors of bone cells). 

There can be increases in calcium and phosphorus loss because of effects on both the kidney and the bowel, with increased excretion and reduced resorption (131). Tetany, which has been seen in patients receiving high-dose longterm intravenous glucocorticoids, has been explained as being due to hypocalcemia, and there are also effects on bone. Tetany has also been reported in a patient with latent hyperparathyroidism after the administration of a glucocorticoid (122). 

KIDNEYS BLOOD UREA NITROGEN, SODIUM, CHLORIDE, PHOSPHORUS, CALCIUM, POTASSIUM, URIC ACID, C02, CREATININE/BUN RATIO HEART TRIGLYCERIDES, CHOLESTEROL, SGPT, SGOT, POTASSIUM. 

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