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1. ?eta�???s�?? f?sf???? S????a � ?a?ade??�ata ?a? p???? ???a ?t?s?? ?ete?pa?de?t??? Se�?????? ?????, ??e?t????t?? & ??e?�as???? ?s????p?a? 5? Se�?????? St??????? t?ap??? IV: ?eta�???s�?? f?sf???? ???ed?e??: ?. G??�e???, S. Spa?a 23-24 Septe��???? 2011 ???st? ???????

2. ?eta�???s�?? f?sf???? ?? a?af?????e; F?s??????a t?? ?s??????? t?? f?sf???? (e???e??? p??s????, ap????f?s?, ap?????s?, ?ata??�?). G?a???t?? ?????e??? � ??�????? ???�?s? t?? ?�???stas?a? t?? f?sf????. ??????�?d?? ??�????? �?p?f?sfata?�?a. ?at?p?d?? ??sta? �?pe?f?sfata?�?a. ???t???�pa? Ge?????? F??�a?a ?a? ?pas�est?a?�?a ? ?p?f?sfata?�?a. ???�?? G??????? �S????a � ?a?ade??�ata ?a? p???? ???a. G. ?pa?t?p?????

3. Stellar nucleosynthesis Stable forms of phosphorus are produced in large (greater than 3 solar masses) stars by fusing two oxygen atoms together. This requires temperatures above 1,000 megakelvins.

4. The four allotropic forms (white, red, black and violet) of phosphorus Colorless, waxy white (yellow cut), scarlet (allowing a solution of white phosphorus in Carbone disulfide to evaporate in sunlight), red (granules center left, chunk center right), violet (produced by day-long annealing of red phosphorus above 550 �C) and black (= heating white phosphorus under high pressures 12,000 standard atmospheres) phosphorus Must be kept under water in pure form Very poisonous 50mg fatal dose (white form) Obtained from phosphate rock (apatite, Ca3(PO4)2 ) found in China, Russia, Morocco, Fl, TN, UT, ID At current consumption rates (fertilizers, detergents, pesticides, nerve agents, matches), reserves will be depleted in the next 50 to 100 years Phosphorus is the sixth most abundant element in living organisms. Is found in every cell (Phosphate)!! Phosphate chemical reactions in the living cells: � 2371

5. ? f???s?f??? ????? ?a? ? f?sf???? The 'squared circle' or 'squaring the circle' is a 17th century alchemical glyph or symbol for the creation of the Philosopher's Stone. The Philosopher's Stone was supposed to be able to transmute base metals into gold and perhaps be an elixir of life Phosphorus - Alchemical�Symbols

6. "The Alchymist, In Search of the Philosopher's Stone" painted by Joseph Wright in 1717 Hennig Brand in Hamburg discovers phosphorus in 1669 from his urine. He called the substance he had discovered "cold fire" because it was luminous, glowing in the dark. White phosphorus's natural chemiluminescence produces a rather dim green glow Brand sold his method to Johann Daniel Kraft and Kunckel von Lowenstern from Dresden for 200 thaler (=4191 $) For further payment he also revealed his secret to Gottfried Wilhelm Leibniz (Mr calculus!!) Leibniz, also thinking as an alchemist, mistakenly believed Brand might be able to discover the philosophers' stone by producing a large quantity of phophorus Allies used phosphorus incendiary bombs in World War II to destroy Hamburg, the place where the "miraculous bearer of light" was first discovered The roots and development of the Thaler-sized silver coin date back to the mid-15th century. As the 15th century drew to a close the state of much of Europe's coinage was quite poor because of repeated debasement induced by the costs of continual warfare, and by the incessant centuries-long loss of silver and gold in indirect one-sided trades importing spices and porcelain and silk and other fine cloths and exotic goods from India, Indonesia and the Far East. This continual debasement had reached a point that silver content in Groschen-type coins had dropped, in some cases, to less than five percent, making the coins of much less individual value than they had in the beginning. Countering this trend, with the discovery and mining of silver deposits in Europe, Italy began the first tentative steps toward a large silver coinage with the introduction in 1472 of the lira tron in excess of six grams, a substantial increase over the, roughly, four-gram gros tournois of France. In 1474 a nine-gram lira was issued but it was in 1484 that Archduke Sigismund of Tirol issued the first truly revolutionary silver coin, the half Guldengroschen of roughly 15� (fifteen and a half) grams. This was a very rare coin, almost a trial piece, but it did circulate so successfully that demand could not be met. Finally, with the silver deposits�being mined at Schwaz�to work with and his mint at Hall, Sigismund issued, in 1486, large numbers of the first true Thaler-sized coin, the Guldengroschen (great gulden, being of silver but equal in value to a Goldgulden). The Guldengroschen, nicknamed the guldiner, was an instant and unqualified success. Soon it was being copied widely by many states who had the necessary silver. The engravers, no less affected by the Renaissance than were other artists, began creating intricate and elaborate designs featuring the heraldic arms and standards of the minting state as well as brutally realistic, sometimes unflattering, depictions of the ruler (monarch). By 1518 guldiners were popping up everywhere in central Europe. In Bohemia, a part of the Holy Roman Empire then controlled by the Jagellonian monarchs, a guldiner was minted�of similar physical size but slightly less fineness�that was named the Joachimsthaler from the silver mined by the Counts of Schlick at a rich source near Joachimsthal (St. Joachim's Valley, J�chymov) (now in the Czech Republic) where Thal (Tal) means "valley" in German. Joachim, the father of the Virgin Mary, was portrayed on the coin along with the lion from the Counts' crest. Similar coins began to be minted in neighbouring valleys rich in silver deposits, each named after the particular 'thal' or valley from which the silver was extracted. There were soon so many of them that these silver coins began to be known more widely as 'thaler'. From these earliest 'thalaer' developed the new Thaler � the coin that Europe had been looking for to create a standard for commerce. The original Joachimsthaler Guldengroschen was 1 ounce in weight (27.2�g). The Reichstaler (1566 to 1750) was defined to contain 25.984�g of Silver which was set as the coin of account of the Empire. In the 17th Century, a certain amount of Joachimsthalers was in circulation in the Tsardom of Russia, where it was called Yefimok () - a distortion of its name's first half. 17th-century Thaler coin from Brunswick-Wolfenb�ttel with the traditional woodwose design on coins from the mints in the Harz Mountains The zenith of Thaler minting occurred in the late 16th and 17th centuries with the so-called "multiple Thalers", often called L�sers in Germany. The first were minted in Brunswick, and indeed the majority were struck there. Some of these coins reached colossal size, as much as sixteen normal thalers. The original reason for minting these colossal coins, some of which exceeded a full pound (over 450g) of silver and being over 12�cm in diameter, is uncertain. The name "l�ser" most likely was derived from a large gold coin minted in Hamburg called the Portugal�ser, worth 10 ducats. Some of the silver l�ser reached this value, but not all. Eventually the term was applied to numerous similar coins worth more than a single Thaler. These coins are very rare, the larger ones often costing tens of thousands of dollars, and are highly sought after by serious collectors of Thalers. Few circulated in any real sense so they often remain in well-preserved condition. In the Holy Roman Empire, the Thaler was used as the standard against which the various states' currencies could be valued. One standard introduced by Prussia was the Reichsthaler, which contained one fourteenth of a Cologne mark of silver. In 1754, the Conventionsthaler was introduced, containing one tenth of a Cologne mark of silver. In 1837, the Prussian thaler became part of a currency union which set the value of the southern German gulden at 1.75 per thaler. By 1850, nearly all German states used this standard of Thaler, though with differing subdivisions. In 1857, the Vereinsthaler was adopted by most German states as well as in the Habsburg Empire. Vereinsthalers were issued until 1871 in Germany and 1867 in Austria. Within the new German Empire, vereinsthaler coins circulated as 3-mark pieces until 1908 when they were withdrawn and demonetized. Some old countermarked thalers circulated as emergency coinage in Germany during the inflationary period following its defeat in World War One. The Maria Theresa thaler was still used during the 20th century in Ethiopia and throughout much of the Arab Peninsula. � About � | � Calculator � | � Photo Gallery � | � Resources �Last Update: September 21, 2011Current Silver Gram Bar Values The values below only reflect the intrinsic silver value, not rarity value. As the price of silver increases, smaller gram-sized bars may become more popular (for example, one-ounce coins will not be as affordable). The closing silver price below is used to calculate the silver gram bar value (USD):Silver gram bar calculations use the closing silver price for September 21, 2011: Silver $39.53/oz 0.09DescriptionSilver Value (USD) 1 gram silver bar$1.27The roots and development of the Thaler-sized silver coin date back to the mid-15th century. As the 15th century drew to a close the state of much of Europe's coinage was quite poor because of repeated debasement induced by the costs of continual warfare, and by the incessant centuries-long loss of silver and gold in indirect one-sided trades importing spices and porcelain and silk and other fine cloths and exotic goods from India, Indonesia and the Far East. This continual debasement had reached a point that silver content in Groschen-type coins had dropped, in some cases, to less than five percent, making the coins of much less individual value than they had in the beginning. Countering this trend, with the discovery and mining of silver deposits in Europe, Italy began the first tentative steps toward a large silver coinage with the introduction in 1472 of the lira tron in excess of six grams, a substantial increase over the, roughly, four-gram gros tournois of France. In 1474 a nine-gram lira was issued but it was in 1484 that Archduke Sigismund of Tirol issued the first truly revolutionary silver coin, the half Guldengroschen of roughly 15� (fifteen and a half) grams. This was a very rare coin, almost a trial piece, but it did circulate so successfully that demand could not be met. Finally, with the silver deposits�being mined at Schwaz�to work with and his mint at Hall, Sigismund issued, in 1486, large numbers of the first true Thaler-sized coin, the Guldengroschen (great gulden, being of silver but equal in value to a Goldgulden). The Guldengroschen, nicknamed the guldiner, was an instant and unqualified success. Soon it was being copied widely by many states who had the necessary silver. The engravers, no less affected by the Renaissance than were other artists, began creating intricate and elaborate designs featuring the heraldic arms and standards of the minting state as well as brutally realistic, sometimes unflattering, depictions of the ruler (monarch). By 1518 guldiners were popping up everywhere in central Europe. In Bohemia, a part of the Holy Roman Empire then controlled by the Jagellonian monarchs, a guldiner was minted�of similar physical size but slightly less fineness�that was named the Joachimsthaler from the silver mined by the Counts of Schlick at a rich source near Joachimsthal (St. Joachim's Valley, J�chymov) (now in the Czech Republic) where Thal (Tal) means "valley" in German. Joachim, the father of the Virgin Mary, was portrayed on the coin along with the lion from the Counts' crest. Similar coins began to be minted in neighbouring valleys rich in silver deposits, each named after the particular 'thal' or valley from which the silver was extracted. There were soon so many of them that these silver coins began to be known more widely as 'thaler'. From these earliest 'thalaer' developed the new Thaler � the coin that Europe had been looking for to create a standard for commerce. The original Joachimsthaler Guldengroschen was 1 ounce in weight (27.2�g). The Reichstaler (1566 to 1750) was defined to contain 25.984�g of Silver which was set as the coin of account of the Empire. In the 17th Century, a certain amount of Joachimsthalers was in circulation in the Tsardom of Russia, where it was called Yefimok () - a distortion of its name's first half. 17th-century Thaler coin from Brunswick-Wolfenb�ttel with the traditional woodwose design on coins from the mints in the Harz Mountains The zenith of Thaler minting occurred in the late 16th and 17th centuries with the so-called "multiple Thalers", often called L�sers in Germany. The first were minted in Brunswick, and indeed the majority were struck there. Some of these coins reached colossal size, as much as sixteen normal thalers. The original reason for minting these colossal coins, some of which exceeded a full pound (over 450g) of silver and being over 12�cm in diameter, is uncertain. The name "l�ser" most likely was derived from a large gold coin minted in Hamburg called the Portugal�ser, worth 10 ducats. Some of the silver l�ser reached this value, but not all. Eventually the term was applied to numerous similar coins worth more than a single Thaler. These coins are very rare, the larger ones often costing tens of thousands of dollars, and are highly sought after by serious collectors of Thalers. Few circulated in any real sense so they often remain in well-preserved condition. In the Holy Roman Empire, the Thaler was used as the standard against which the various states' currencies could be valued. One standard introduced by Prussia was the Reichsthaler, which contained one fourteenth of a Cologne mark of silver. In 1754, the Conventionsthaler was introduced, containing one tenth of a Cologne mark of silver. In 1837, the Prussian thaler became part of a currency union which set the value of the southern German gulden at 1.75 per thaler. By 1850, nearly all German states used this standard of Thaler, though with differing subdivisions. In 1857, the Vereinsthaler was adopted by most German states as well as in the Habsburg Empire. Vereinsthalers were issued until 1871 in Germany and 1867 in Austria. Within the new German Empire, vereinsthaler coins circulated as 3-mark pieces until 1908 when they were withdrawn and demonetized. Some old countermarked thalers circulated as emergency coinage in Germany during the inflationary period following its defeat in World War One. The Maria Theresa thaler was still used during the 20th century in Ethiopia and throughout much of the Arab Peninsula. � About � | � Calculator � | � Photo Gallery � | � Resources �Last Update: September 21, 2011Current Silver Gram Bar Values The values below only reflect the intrinsic silver value, not rarity value. As the price of silver increases, smaller gram-sized bars may become more popular (for example, one-ounce coins will not be as affordable). The closing silver price below is used to calculate the silver gram bar value (USD):

7. Evelyn de Morgan: Greek gods Phosphorus and Hesperus -?????a & ???e????? Phosphorus (gr. Eosphoros, l. Lucifer)�and Hesperus(gr. Hesperos, l. Vesper)�are brothers, sons of the rosy fingered goddess of dawn, Eos (latin: Aurora). Phosphorus is the planet Venus�when it appears�as the morning star (???e?????). Hesperus (?p?spe??t??) is the planet Venus�when it appears as�the evening star. The early greeks believed these�to be�two distinct astronomical bodies and assigned two distinct dieties to the planet as it appeared respectively�in the morning�and evening.�The later�greeks adopted the Babylonian view that the morning and evening star were�a single�wandering star and associated it with the goddess Aphrodite(l. Venus). Like the goddess Venus and the stars themselves,� Phosphorus and Hesperus are eternally young and beautiful. Only their mother Eos (Dawn) and�her sister and brother,�Selene (the moon) and Helios(the Sun), shine more brightly in the heavens. It is Phosphorus, the�bringer of light, who�wakes his mother Eos from her sleep in the depths of the sea each morning and ushers in the dawn. It is Hesperus who ushers in the evening at dusk. Hesperus�brings all good things home�at the end of the day. He is the god of the hearth and domestic happiness. One might curse Phosphorus when getting up in the morning to go to work and bless Hesperus in the evening when returning to the comfort of home. 

8. ?a?a???? F?sf???? ?at? Brand Evaporate human urine ?black residue?leave it for a few months Then heat the residue with sand? condense the variety of gases and oils, driving off in water The final substance to be driven off, condensing as a white solid, is phosphorus !!! ?a?a????: 1100 L ????? (60 ???�?de? a???�?st??? ???a !!) ? 60 gr

9. Functions of phosphate Hydroxyapatite Phospholipids Adenosine triphosphate (ATP) and creatine phosphate (intermediate in glycolysis and oxidative phosphorylation) Nucleic acids and nucleoproteins Phosphorylation of proteins 2,3-Diphosphoglycerate (glycolysis byproduct ) Inorganic phosphate Bone structure (85% of P in body ) Structure of cell membranes Energy storage and metabolism Genetic translation (DNA) and protein synthesis (RNA) Key regulatory mechanism; activation of enzymes, cell-signaling cascade Modulates oxygen release by hemoglobin Acid-base buffer (Intracellularly and in the renal tubules where it aids in the excretion of hydrogen ions)

10. P is essential element for metabolic processes ATP +ADP= remains fairly constant The Harris-Benedict equation for BMR: For men: (13.75 x w) + (5 x h) - (6.76 x a) + 66 For women: (9.56 x w) + (1.85 x h) - (4.68 x a) + 655 The Mufflin equation for RMR: For men: (10 x w) + (6.25 x h) - (5 x a) + 5 For women: (10 x w) + (6.25 x h) - (5 x a) - 161 Where: w = weight in kg h = height in cm a = age Body Composition The Harris-Benedict equation for BMR: For men: (13.75 x w) + (5 x h) - (6.76 x a) + 66 For women: (9.56 x w) + (1.85 x h) - (4.68 x a) + 655 The Mufflin equation for RMR: For men: (10 x w) + (6.25 x h) - (5 x a) + 5 For women: (10 x w) + (6.25 x h) - (5 x a) - 161 Where: w = weight in kg h = height in cm a = age Body Composition

11. Phosphorylation- Photophosphorylation The addition of a phosphate (PO4) group to another molecule, including any protein, is phosphorylation. Many enzymes and receptors are switched "on" or "off" by phosphorylation. Phosphorylation is catalyzed by specific protein kinases. Phosphorylation of any amino acid having a free hydroxyl group on a given protein can change the function, association, or localization of that protein. Dephosphorylation is catalyzed by phosphatases. Oxidative phosphorylation is the process of oxidizing nutrients to produce adenosine triphosphate (ATP). Substrate-level phosphorylation forms ATP by the direct transfer of a phosphate group to adenosine diphosphate (ADP) from a reactive intermediate. Photophosphorylation uses solar energy to synthesize ATP. Phosphorylation of sugars allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter.

12. Phosphate reserves A well-fed adult in the industrialized world consumes and excretes: 1-3 g of phosphorus per day in the form of phosphate (2-6 x 1022 molecules). Phosphorus in a "standard man" of 70�kg : 780 g or 1.1% (as 1.52 x 1025 molecules of phosphate) 1.4 g/kg (98 g, 1.9 x 1024 molecules of phosphate) are present in soft tissue 675 gr (1.33 x 1025 molecules of phosphate) in mineralized tissue such as bone and teeth 0.1% of body phosphate (about 2 x 1022 molecules) circulates in the blood this amount reflects the amount of phosphate available to soft tissue cells Blood plasma contains orthophosphate (as HPO42-) and H2PO4- in the ratio of about 4:1.

13. PO43� : molar mass= 94.97 g/mol

15. ???te �?a a?e??da

16. Phosphorus-Phosphates: Normal serum levels 0.80 to 1.45 mmol/L (2.5 to 4.5 mg/dl) Geerse et al. Critical Care 2010, 14:R147. Alternative Names: Phosphorus - serum; HPO4-2, PO4-3; Inorganic phosphate; Phosphorus blood test The serum concentration of phosphate may not reflect true phosphate stores. VARIES significantly with age!!! Mammaliam cell internal phosphate levels= 75 mEq/L. ISF =4 mEq/L

17. Phosphate metabolism and causes of hypophosphatemia

18. Prevalence and/or incidence of hypophosphatemia Prevalence versus incidence: Prevalence and incidence are different measures of a disease's occurrence. The "prevalence" of a condition means the number of people who currently have the condition, whereas "incidence" refers to the annual number of people who have a case of the condition. These two measures are very different. A chronic incurable disease like diabetes can have a low incidence but high prevalence, because the prevalence is the cumulative sum of past year incidence rates. A short-duration curable condition such as the common cold can have a high incidence but low prevalence, because many people get a cold each year, but few people actually have a cold at any given time (so prevalence is low and is not a very useful statistic). To understand prevalence versus incidence, consider these examples (which over-simplify but are still hopefully useful): Prevalence versus incidence: Prevalence and incidence are different measures of a disease's occurrence. The "prevalence" of a condition means the number of people who currently have the condition, whereas "incidence" refers to the annual number of people who have a case of the condition. These two measures are very different. A chronic incurable disease like diabetes can have a low incidence but high prevalence, because the prevalence is the cumulative sum of past year incidence rates. A short-duration curable condition such as the common cold can have a high incidence but low prevalence, because many people get a cold each year, but few people actually have a cold at any given time (so prevalence is low and is not a very useful statistic). To understand prevalence versus incidence, consider these examples (which over-simplify but are still hopefully useful):

19. Reported incidence of hypophosphatemia Table 2 Reported incidence of hypophosphatemia in different patient samplesTable 2 Reported incidence of hypophosphatemia in different patient samples

20. Hypophosphatemia Causes: Decreased intake of phosphorus Nutritional deficiency Anorexia Malnutrition Impaired absorption (IBD, chronic diarrhea, celiac dz) Premature infants (? needs compared to term infants) Low phosphorus formula Antacids and other phosphate binders (prevent absorption) Renal failure treatment Antacid overuse

21. Hypophosphatemia Causes: Increased Excretion Hyperparathyroidism Parathyroid hormone�related peptide (malignancy) Tumor-induced osteomalacia Hypophosphatemic rickets Fanconi syndrome Dent disease (x-linked defective chloride channel) Mutations in sodium-phosphate cotransporter Volume expansion and intravenous fluids Metabolic acidosis (phosphorus shifts out of cells then excreted by kidney) Diuretics Others

22. Hypophosphatemia Causes: Transcellular Shifts Overall- increased intracellular use of phosphorus Glucose infusion?insulin release Insulin? shift of glucose and phosphorus into cells Refeeding? anabolic state leads to ?cellular demand for phos Usually in first 5 days of refeeding (34% of critically ill) Total parenteral nutrition (insufficient supplementation) Respiratory alkalosis? ?intracellular pH stimulates intracellular metabolism and increased phos use Tumor growth (leukemia/lymphoma due to ? use by tumors) Bone marrow transplantation Hungry bone syndrome (use of phos/ca/mg) after parathyroidectomy

23. Hypophosphatemia Causes: Multifactorial Vitamin D deficiency impaired intestine absorption hyperPTH causes ? renal phosphorus losses Sepsis� Dialysis�

24. Diagnostic Testing The history and basic laboratory evaluation (serum calcium, magnesium, and potassium) often suggests the etiology should investigate nutrition, medications, and familial disease. Vit D levels (1,25- and 25-), calcium, and PTH differentiate the vitamin D deficiency disorders and X-linked hypophosphatemic rickets. Hyperparathyroidism has ? plasma PTH and calcium levels. Low magnesium = poor nutrition. Arterial blood gas: if respiratory alkalosis is suspected Urinary phosphorus determination confirms the presence of renal phosphate wasting. Urinalysis (fanconi will show renal glycosuria, aminoaciduria, type II renal tubular acidosis, hypouricemia, and hypophosphatemia.)

25. DIAGNOSIS OF HYPOPHOSPHATEMIA History & S. PO4 24 hr urine collection Urine phosphate excretion If renal P wasting in not the cause of hypophosphatemia Daily P excretion should be<100mg/d. FEPO4 <5% normally Calculation: FEPO4=(U PO4 * Pcr) * 100/ P PO4* Ucr DD of hypoP with low FEPO4 Increased cellular uptake Chronic diarrhea Causes of high PO4 excretion-Renal PO4 wasting Hyperparathyroidism Proximal renal tubular defect.

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27. Treatment Intravenous therapy (severe deficiency or cannot tolerate oral) Sodium phosphate or potassium phosphate Choice based on K+ level Starting doses are 0.08�0.16 mmol/kg over 6 hr. The oral preparations of phosphorus are available with various ratios of sodium and potassium. Oral maintenance doses are 2�3 mmol/kg/day in divided doses. (cause diarrhea) Increasing dietary phosphorus is the only intervention needed in infants with inadequate intake. Certain diseases require specific therapy. Nutritional vitamin D deficiency Vitamin D supplementation, not phosphorus, is the principal therapy X-linked hypophosphatemic rickets Combination of 1,25-dihydroxyvitamin D and oral phosphorus.

28. Intravenous treatment of hypophosphatemia

29. CRRT : Phosphate and Magnesium Hypophosphatemia and Hypomagnesiemia occur in almost all patients on CRRT for = 48 hours. Management: Routinely supplement patients with IV PO4 and MgSO4 on regular basis: Sodium phosphate 20 mmol in 250 mls IV fluid over 3-4 hours q 8-12 hours Magnesium sulphate 2 gm IV q 8-12 H,

30. Phosphate Control in ESRD

31. Practice Case 1 A 15-year-old girl is admitted to your facility with severe anorexia nervosa and amenorrhea. She weighs 35 kg and is 160 cm tall. She has bradycardia and orthostatic hypotension. You plan to stabilize her medically and begin nasogastric tube feeding. Of the following, the electrolyte abnormality that is MOST likely to occur during the first week of her treatment is A. hypercalcemia B. hyperphosphatemia C. hypocalcemia D. hyponatremia E. hypophosphatemia Preferred Response: E The girl described in the critique is severely malnourished and about to undergo intensive nutritional rehabilitation with enteral feeding. Although this therapy is lifesaving, it also may result in refeeding syndrome. In this syndrome, malnourished patients given oral, enteral, or intravenous nutrition develop fluid retention and electrolyte abnormalities. The most common electrolyte abnormality reported is hypophosphatemia, which can occur in approximately 25% of patients who have anorexia nervosa during refeeding. Other electrolyte and micronutrient abnormalities, including hyponatremia, hypocalcemia, hypokalemia, hyperglycemia, and thiamine deficiency, also may occur, but are less prevalent than hypophosphatemia. Hypercalcemia and hyperphosphatemia generally do not occur. With careful monitoring of electrolytes and slow refeeding, signs and symptoms of refeeding syndrome can be avoided. However, the clinical manifestations include edema, muscle weakness, and cardiac arrhythmias. The precise mechanism by which phosphorus levels are lowered during refeeding has not yet been characterized fully. Malnourished patients are depleted in total body phosphorus, despite normal serum concentrations. The carbohydrate challenge during refeeding induces the release of insulin, which causes fluid and electrolyte shifts. In addition, malnourished patients being refed synthesize the phosphate-rich compounds creatine phosphokinase, 2,3 diphosphoglycerate, and adenosine triphosphate. Thus, total body stores of phosphorus may be depleted even further during energy synthesis. To minimize the risk of refeeding syndrome, supplemental feedings should be introduced gradually to malnourished patients (beginning at 25% of recommended calories and advancing to full calories over 5 to 7 days). In addition, serum electrolytes, blood glucose, calcium, phosphorus, and magnesium should be measured at least daily for the first week of feeding. Many centers automatically prescribe a phosphorus supplement (500 mg twice a day) to patients who have anorexia nervosa and are being refed. Preferred Response: E The girl described in the critique is severely malnourished and about to undergo intensive nutritional rehabilitation with enteral feeding. Although this therapy is lifesaving, it also may result in refeeding syndrome. In this syndrome, malnourished patients given oral, enteral, or intravenous nutrition develop fluid retention and electrolyte abnormalities. The most common electrolyte abnormality reported is hypophosphatemia, which can occur in approximately 25% of patients who have anorexia nervosa during refeeding. Other electrolyte and micronutrient abnormalities, including hyponatremia, hypocalcemia, hypokalemia, hyperglycemia, and thiamine deficiency, also may occur, but are less prevalent than hypophosphatemia. Hypercalcemia and hyperphosphatemia generally do not occur. With careful monitoring of electrolytes and slow refeeding, signs and symptoms of refeeding syndrome can be avoided. However, the clinical manifestations include edema, muscle weakness, and cardiac arrhythmias. The precise mechanism by which phosphorus levels are lowered during refeeding has not yet been characterized fully. Malnourished patients are depleted in total body phosphorus, despite normal serum concentrations. The carbohydrate challenge during refeeding induces the release of insulin, which causes fluid and electrolyte shifts. In addition, malnourished patients being refed synthesize the phosphate-rich compounds creatine phosphokinase, 2,3 diphosphoglycerate, and adenosine triphosphate. Thus, total body stores of phosphorus may be depleted even further during energy synthesis. To minimize the risk of refeeding syndrome, supplemental feedings should be introduced gradually to malnourished patients (beginning at 25% of recommended calories and advancing to full calories over 5 to 7 days). In addition, serum electrolytes, blood glucose, calcium, phosphorus, and magnesium should be measured at least daily for the first week of feeding. Many centers automatically prescribe a phosphorus supplement (500 mg twice a day) to patients who have anorexia nervosa and are being refed.

32. A 56 yrs ?. Referred from another hospital with H/o LOC ? treated for CVA , intubated because of respiratory distress and low GCS (7/15). On regaining conscious, he was confused and developed fever with restlessness. Right 3rd nerve Palsy, was able to move all 4 limbs. Paucity of movements and Babinski on right side. Right pupil: 3mm, Left pupil:2mm CT scan Head : Small Area of bleed in left occipito-temporal region with mild surrounding edema. Infarcts in right side of midbrain and pons Type 2DM-6 yrs, HTN-6 yrs, CAD & CABG (2004). Chronic smoker & chronic alcoholic(150g/d for >30 years) P:92 b/m. BP : 142/80 mmHg. Echo : EF : 35 %, hypokinesia of LV segments. Practice Case 2

33. Investigations upon admission Urea : 51 mg% Cr :1.1 mg% Na+ : 140 meq/l K+ : 3.4 meq/l Hb :13 g% Tc : 8,800 cells/c.mm. ABG : mild respiratory alkalosis Urine analysis 1 + proteinuria 2-4 RBC�s & WBC� s

34. Continued Over 48 hours the sensorium improved marginally, but over next 12 hours deteriorated markedly without any apparent reason. S. Ca2+ :8.2 mg% S. PO4- :1.1 mg%, coincided with the time in deterioration in sensorium. The test report was not given attention for 12 hours (Repeat Sr PO4: 1.3 mg%) 24 hrs urine Ca2+ : 101 mg/day 24 hrs urine PO4 : 891 mg/day( upto 1400mg is normal) FEPO4 was : 25 %.(expected was close to 0) 25 OH VIT D : 25.5 ng/l (7.6-75) S. iPTH : 73 pg/ml (10-69)

35. Pt�s Hypophosphatemia treatment We treated with IV potassium phosphate: 5ml in 250ml of NS over 6 hrs on day 1 & 2. Next day his S. PO4 was 2.1mg% We also noticed that his sensorium had improved significantly. Continued on oral sodium phosphate

36. The happy end !! Subsequent day,his sensorium worsened with 1 episode of seizure .But his PO4 was 2.4 mg%. MRI Brain revealed increase in the size of intracranial bleed with fresh infarcts in PCA territory. He was treated with anticonvulants, antiedema measures and antibiotics in suspicion of sepsis. On day 5, his PO4 level was built to 4.2mg%, at which point NaPO4 was discontinued. His azotemia resolved. He remained ventilator dependent for 19 days, developed VAP (resolved). CONDITION ON DISCHARGE Alert, conscious Ptosis of RE Mild residual right hemiparesis He was able to walk and eat by himself

37. 67 yrs ?. ???????�e?? ?st?????: ?a??sa???a, ??f?s?, ??p??s�a (� pa?/?�??a), ?p???a t?? ?p???, ?p??tas? (micardis 1/2x1), ???, S? ( glucophage 1x2, solosa 1x1), ?F? ( xanax 0,25x2) ?????a��at?s�??? ep?��as? ??a ??????????? (29/6/11) se ?d??t??? ??????? ? �etaf??? se ??F ???? ??? ??? (?p??a?�?a)? d?as?????s? � e?sa???? se ??T (1/7/11)? �etaf??? st?? ??? ??T (4/7/11) GCS 11T, ?atast???, e�p??et?? 38? C ??�?d??a�??? ast??e?a ?p? ???ad?e?a???? 15 ?/?ept? ??G- f?e�???��??, RBBB ??ap?e?st??? a?ep???e?a ?p? ???, FiO2 0.9-1.0, PEEP 10 ??????spas�??, �e??s? a?ap?. ??????s�at?? a??ste?? ?/? ???a??? - p????ate?e?tas?a a??ste?? ??????s? �e??�??? ?p? lasix ?????a � e?te????? ???? ?p??????, f??e? 2 pa???ete?se?? ??a??�?d? ap? ?d??t??? ??????? 4 ?�??e? �et? ap? ?????a��at?s�??? ep?��as? ??a ??????????? (29/6/11), ??a a?ap?e?st??? a?ep???e?a/???�??? t?? a?ap?e?st????/s?pt??? shock. Practice Case 3

38. 77 ?�??e? st? ??T

39. ?e????? ???s?�?? ?p?????s�??

40. Hyperphosphatemia Causes: Increased Intake Enemas and laxatives Fleet enemas have high phosphorus content Sodium phosphorus laxatives Don�t use in small kids! Increased in ileus and hirschprung�s disease Cow's milk in infants Higher phosphorus content than human breastmilk Treatment of hypophosphatemia Overly aggressive treatment Vitamin D intoxication Excessive GI absorption of calcium and phosphorus Hypercalcemia suppresses PTH release Phosphorus excretion is then decreased at kidney ?phos resorption at proximal convoluted tubule

41. Hyperphosphatemia Causes: Decreased Excretion Renal failure Hypoparathyroidism or pseudohypoPTH ? Phosphorus resorption at Prox Conv Tubule Acromegaly ? Phosphorus resorption at Prox Conv Tubule due to GH Hyperthyroidism Increased thyroxine=? Phos resorption at PCT Increased Bone resorption- ?phos, ? Ca+ Tumoral calcinosis with hyperphosphatemia ?renal phos excretion heterotopic calcifications

42. Hyperphosphatemia Causes: Transcellular Shifts Tumor lysis syndrome Cellular breakdown with release of contents ?phos, ? K+, ?uric acid, ?calcium Rhabdomyolysis Muscle cell breakdown with myoglobin release ?phos, ? K+, ?CPK) Acute hemolysis Red blood cell breakdown ?phos, ? K+, ? indirect bilirubin, ?LDH Diabetic ketoacidosis and lactic acidosis During acidosis, phosphorus is shifted from the intracellular to the extracellular space

43. Hyperphosphatemia:Clinical Manifestations Hypocalcemia Tissue deposition of calcium-phosphorus salt Inhibition of 1,25-dihydroxyvitamin D production Decreased bone resorption. Symptomatic hypocalcemia is most likely when phosphorus increases rapidly diseases predisposing to hypocalcemia are present chronic renal failure rhabdomyolysis). Systemic calcification Solubility of phosphorus and calcium in the plasma is exceeded. Inflamed conjunctiva- foreign body feeling, erythema, and injection. (BOBBY) Hypoxia from pulmonary calcification Renal failure from nephrocalcinosis.

44. Diagnostic Testing Assess renal function: Bun and creatinine. Focus history on intake of phosphorus and the presence of chronic disease. If suspect rhabdomyolysis, tumor lysis, or hemolysis Check potassium, uric acid, calcium, LDH, bilirubin, and CPK If mild hyperphosphatemia and sign hypocalcemia check serum PTH level Distinguishes between hypoparathyroidism and pseudohypoparathyroidism.

45. Treatment Depends on its severity and etiology. Dietary phosphorus restriction- in mild hyperphosphatemia Intravenous fluids- enhance renal excretion if kidney function is intact. Oral phosphorus binder- in significant hyperphosphatemia Prevents absorption of dietary phos Removes phos from the body by binding what is normally secreted and absorbed by GI tract Binders containing aluminum hydroxide or use calcium carbonate if also hypocalcemic. Aluminum-containing binders NOT used in CRF because of aluminum toxicity. Esp if taking oral citrate, which ? gastrointestinal absorption of aluminum. Preservation of renal function-high urine flow permits continued excretion Dialysis directly removes phosphorus from the blood in ESRD only an adjunct to dietary restriction and phosphorus binders dialysis is not efficient enough to keep up with normal dietary intake.

47. S?�pe??s�ata ? ?pe?f?sfata?�?a ?a? ?p?f?sfata?�?a ?e? e??a? sp???e? se �?a ??T ???a? a?t?�et?p?s?�e? ??t?t?te? ?e? �p????�e ?a p??�e p??a e??a? ? s?��et??? t??? st?? ??s???t?ta ?a? ???t?t?ta St?? ??T p??ta ?p???e? ? p??a??t?ta ?a �?e?? ??a pe??stat??? p?? ?a ta ??e? ??a!!! ?? pe??a�a t? ???e? ? f?s? ?a? e�e?? a???p????�e ta ap?te??s�ata