Phosphate ions, blood

A. Increased levels of blood phosphate ion interact with sensors on the membrane of parathyroid cells to stimulate parathyroid hormone... 

The H2PO4/HPO4 pair is the principal buffer in cells. In blood, phosphate ion levels are inadequate for buffering, and a different system operates. 

CycHc adenosine monophosphate (cAMP), produced from ATP, is involved in a large number of ceUular reactions including glycogenolysis, Hpolysis, active transport of amino acids, and synthesis of protein (40). Inorganic phosphate ions are involved in controlling the pH of blood (41). The principal anion of interceUular fluid is HP (Pig. 3) (41). 

The Ca(Il) coaceatratioa ia blood is closely coatroUed aormal values He betweea 2.1 and 2.6 mmol/L (8.5—10.4 mg/dL) of semm (21). The free calcium ion concentration is near 1.2 mmol/L the rest is chelated with blood proteias or, to a lesser extent, with citrate. It is the free Ca(Il) ia the semm that determines the calcium balance with the tissues. The mineral phase of bone is essentially ia chemical equiUbrium with calcium and phosphate ions present ia blood semm, and bone cells can easily promote either the deposition or dissolution of the mineral phase by localized changes ia pH or chelating... 

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. 

SBF is a solution that has inorganic ion concentrations similar to those of human blood plasma but does not contain any cells or protein. A brief summary of SBF, introduced by Cho et al. [17], follows. The ion concentrations of SBF are given in Table 11.1 [17]. The pH of SBF is typically adjusted to 7.25 or 7.40 at 36.5 °C. This fluid is a metastable solution containing calcium and phosphate ions supersaturated with respect to hydroxyapatite. SBF is prepared by successively dissolving the reagent-grade chemicals in ultra-pure water in the order given in Table 11.2 [17]. Each new chemical is added after the previous one has completely dissolved. The temperature... 

I he kidneys are sometimes called the master chemists of the body. They work to maintain the constant composition of the hlood hy helping to balance water and the various ions that are present in the blood. A very important equilibrium in the blood, which the kidneys help to control, involves calcium ions and phosphate ions. 

This equilibrium sometimes causes problems, however. For example, calcium phosphate helps to give bones their rigidity. If the kidneys remove too many phosphate ions from the blood due to disease, the position of equilibrium shifts to the left, as predicted by Le Chatelier s principle. More calcium phosphate dissolves in the blood, reducing bone density. The loss of too much calcium phosphate can lead to osteoporosis. 

Laboratory assessment of the composition of the blood plasma is often carried out in clinical chemistry. Among the electrolytes, there is a relatively high concentration of Na"", Ca and Cl ions in the blood in comparison with the cytoplasm. By contrast, the concentrations of IC, Mg "", and phosphate ions are higher in the cells. Proteins also have a higher intracellular concentration. The electrolyte composition of blood plasma is similar to that of seawater, due to the evolution of early forms of life in the sea. The solution known as physiological saline" (NaCl at a concentration of 0.15 mol L ) is almost isotonic with blood plasma. 

Bone is an extremely dense, specialized form of connective tissue. In addition to its supportive function, it serves to store calcium and phosphate ions. In addition, blood cells are formed in the bone marrow. The most important mineral component of bone is apatite, a form of crystalline calcium phosphate. 

The most downfield resonance is that of inorganic phosphate ion, (P04)v (abbreviated P,). When cells carry out their normal metabolic function, phosphate is cleaved from ATP to produce P,. The energy status of cells may therefore be gauged by measuring, for instance, the PCr/P, ratio. Cells with a low value of this ratio are energy depleted, which might result from insufficient blood supply (ischemia) or some metabolic disorder. 

An artificial kidney is a device that removes water and waste metabolites from blood. In one such device, the hollow fiber hemodialyzer, blood flows from an artery through the insides of a bundle of hollow cellulose acetate fibers, and dialyzing fluid, which consists of water and various dissolved salts, flows on the outside of the fibers. Water and waste metabolites—principally urea, creatinine, uric acid, and phosphate ions—pass through the fiber walls into the dialyzing fluid, and the purified blood is returned to a vein. 

Phosphorus, in the form of electrically charged phosphate ions, has a significant influence on water balance and osmotic pressure in the body. Phosphate in the blood helps maintain the acid-alkaline balance. An acid phosphate (monosodium phosphate) works with an alkaline phosphate (disodium phosphate) to stabilize this balance. 

Dissolved calcium and phosphate ions may remain soluble despite their concentrations exceeding the solubility product in blood plasma and stromal extracellular (interstitial) fluid where the pH is just above 7 (Sect. 3.3.1). In blood plasma, mineralization is prevented by polyanions, especially albumin, citrate, and pyrophosphate (PPi), which chelate calcium ions and prevent their precipitation with monohydrogen phosphate ions (orthophosphate, Pi, or HP042-). Pyrophosphate (PPi) inhibits the premature aggregation of calcium with monohydrogen phosphate ions in mineralizing tissues and interstitial fluid throughout the body (Fig. 9.1b). 

Osteoblasts secrete osteoid, a matrix rich in type I collagen fibers and vesicles. Precipitation of calcium phosphate is inhibited by a high concentration of pyrophosphate in stromal interstitial fluids, and a high concentration also of albumin and citrate in blood plasma. Pyrophosphate is derived from (1) transport out of the cytosol, and (2) synthesis from nucleoside triphosphates in the stromal interstitial fluid that permeates the osteoid matrix. Precipitation occurs only when calcium and phosphate ions are taken up into vesicles whose inner membrane is composed of phosphatidylserine. The high concentration of calcium and phosphate ions in the vesicle is mediated by annexin and type HI Pi Na-dependent transporters. This overwhelms the pyrophosphate and nucleation occurs. As the precipitate grows and ruptures the membrane, tissue-nonspecific alkaline phosphatase is activated to remove pyrophosphate from the osteoid matrix fluid so that calcium phosphate precipitates around phosphorylated serine residues within the collagen fibers. 

The answer is d. (Murray, pp 298-307. Scriver, pp 1471-1488. Sack, pp 217—218. Wilson, pp 361—384.) The sum of the major cations in blood (Na plus K+) minus the sum of the major anions (HCO3 plus Ch) is called the anion gap (filled by phosphate ions, negatively charged proteins, etc.). An anion gap over 20 suggests the presence of an abnormal anion, such as acetoacetate, which occurs in diabetics. The anion gap in... 

Phosphorus is absorbed by animals from food (and by plants from the soil (Chapter 12.2)) in the form of phosphate ions HPO and H2PO4. In animals some of the element is found in this form in blood, urine and tissue fluids, but mostly as inorganic calcium salts in bones and teeth. The remaining phosphorus is present as organic phosphate , which is almost all in the form of numerous mono-and di-esters in which fully oxidised P is almost always linked indirectly to carbon through P-O-C bonds. In a few compounds P-NH-P linkages are formed. 

When the calcium concentration drops below normal, the parathyroid gland secretes parathyroid hormone (PTH). This hormone stimulates bone-reabsorbing cells (i.e., osteocytes and osteoblasts), which cause an increase in calcium and phosphate ions in the extracellular fluid. PTH in association with vitamin D also can stimulate the absorption of calcium indirectly from the intestine and cause the kidney to conserve calcium ions and excrete phosphate ions. Therefore, any damage to the parathyroid gland or the kidneys or failure of the body to produce 1,25-dihydroxy vitamin D will prevent mobilization of calcium from the bones and intestine to the blood plasma. This will lead to hypocalcemia. 3... 

The phosphorus levels of the blood are high in secondary hyperparathyroidism. This is likely to result from phosphorus retention due to tubular damage. Reduced phosphorus filtration through the glomeruli has been eliminated. In renal insufficiency, the renal tubules either resorb more phosphorus than normal, or the phosphorus secretion is blocked. Since tubular secretion of phosphorus has not been established conclusively, one must assume that the phosphorus retention results from accelerated resorption. Calcium and phosphate ions are maintained in equilibrium in the blood. The calcium levels in the blood will be reduced in the presence of higher levels of phosphate ions, but again, the theory postulates that calcium levels are low in patients with renal insufficiency. 

Normal serum calcium level in man is 4.5-5.5 x IO m. About 40 % of this is bound to protein (nondialyzable) and is not in rapid equilibrium with the solution. Thus, we use about 3 x 10 m for the available calcium(II). Similarly, there is about 1 x 10 available phosphates, mainly H2PO4 and HPO (see a diagrams). This is higher in children during bone-forming years. First, we might ask whether these levels are near or above saturation for the solids listed above. To find the appropriate phosphate ion concentration, we need only multiply the total available phosphates by the a value for blood serum pH, 7.40. We use the Kielland table (Appendix A-1) values of activity coefficients to adjust the K values to / = 0.1 M. The / values are for Ca ", 0.405 for P04 , 0.095 for HPO , 0.37 for OH , 0.755. This produces new conditional K values for the set(ll-5a)-(ll-5e) ... 

Caldum is a silvery white, malleable and ductile metal that bums with a yellow-red flame. In air it forms a white coating of oxide and nitride and it reacts violently with water. The element is an essential element for Kfe as a transmitter of nerve impulses and for clotting of blood. Its ions may bind to negatively charged groups in proteins and can in this way switch the activity of en2ymes on and oflF . Apatite, a calcium phosphate, builds skeletons and teeth. 

Lanthanide metal ions, Ln +, can exchange with, and mimic the function of, Ca + ions in the human body. Lanthanum carbonate is administered as chewable tablets under the tradename of Fosrenol to patients with particularly high levels of phosphate ions in the blood. However, there are significant gastrointestinal side-effects, and more soluble... 

Blood contains several substances that minimize changes in its acidity by reacting with either an acid or a base. One of these is the hydrogen phosphate ion, HP04. Write one equation showing this species acting as a Brpnsted—Lowry acid and another in which the species acts as a Brpnsted— Lowry base. 

An important component of blood is the buffer combination of dihydrogen phosphate ion and the hydrogen phosphate ion. Consider blood with a pH of 7.44. 

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