Μεταβολισμός φωσφόρου Μεταβολισμός φωσφόρου Σχόλια – ΠαραδείγματαΣχόλια – Παραδείγματα και και

πολλά άλλαπολλά άλλαΕτήσιο Μετεκπαιδευτικό ΣεμινάριοΕτήσιο Μετεκπαιδευτικό Σεμινάριο

Υγρών, Ηλεκτρολυτών & Οξεοβασικής ισορροπίαςΥγρών, Ηλεκτρολυτών & Οξεοβασικής ισορροπίας 5ο Σεμινάριο5ο Σεμινάριο

Στρογγυλό τραπέζι Στρογγυλό τραπέζι IVIV: : Μεταβολισμός φωσφόρουΜεταβολισμός φωσφόρου

ΠροεδρείοΠροεδρείο: : Δ. Γούμενος,Δ. Γούμενος, Σ. ΣπαΐαΣ. Σπαΐα23-24 Σεπτεμβρίου 201123-24 Σεπτεμβρίου 2011

Βλάστη Κοζάνης Βλάστη Κοζάνης Σάββατο, 24 Σεπτεμβρίου 2011 10.00-11.40

Καθηγητής Γεώργιος Ι. ΜπαλτόπουλοςΔιευθυντής ΠανΜΕΘ ΓΝ Οι ΄Αγιοι Ανάργυροι

Μεταβολισμός φωσφόρου Μεταβολισμός φωσφόρου Τι αναφέρθηκε;Τι αναφέρθηκε;

Φυσιολογία του ισοζυγίου του φωσφόρου Φυσιολογία του ισοζυγίου του φωσφόρου (εξωγενής πρόσληψη, απορρόφηση, απέκκριση, (εξωγενής πρόσληψη, απορρόφηση, απέκκριση, κατανομή). κατανομή). Γιαννάτος ΕυάγγελοςΓιαννάτος Ευάγγελος

    Ορμονική ρύθμιση της ομοιοστασίας του Ορμονική ρύθμιση της ομοιοστασίας του φωσφόρου. φωσφόρου. Οικονομίδου ΔομινίκηΟικονομίδου Δομινίκη

  Υποφωσφαταιμία. Υποφωσφαταιμία. Κατωπόδης ΚώσταςΚατωπόδης Κώστας   Υπερφωσφαταιμία. Υπερφωσφαταιμία. Κουτρούμπας ΓεώργιοςΚουτρούμπας Γεώργιος Φάρμακα και υπασβεστιαιμία ή υποφωσφαταιμία. Φάρμακα και υπασβεστιαιμία ή υποφωσφαταιμία.

Λιάμης ΓιώργιοςΛιάμης Γιώργιος   Σχόλια – ΠαραδείγματαΣχόλια – Παραδείγματα και πολλά άλλα. και πολλά άλλα. Γ. Γ.

ΜπαλτόπουλοςΜπαλτόπουλος

Stellar nucleosynthesisStellar nucleosynthesis Stable forms of phosphorus are produced in large Stable forms of phosphorus are produced in large

(greater than 3 solar masses) stars by fusing two (greater than 3 solar masses) stars by fusing two oxygen atoms together.oxygen atoms together.

This requires temperatures above 1,000 This requires temperatures above 1,000 megakelvins.megakelvins.

P4 molecule P2 molecule

Atomic number 15Atomic number 15Atomic weight 30.974- Atomic weight 30.974- 31PPTwo most common isotopes: Two most common isotopes: 32P and P and 33P (P (24P up to P up to 46PP))Density 1.82 g/cm3Density 1.82 g/cm3

The four allotropic forms (white, The four allotropic forms (white,

red, black and violet)red, black and violet) of phosphorusphosphorus

ColorlessColorless,, waxy white waxy white ( (yellow cutyellow cut), ), scarletscarlet ( (allowing a solution of white phosphorus inallowing a solution of white phosphorus in Carbone disulfide to evaporate in sunlightCarbone disulfide to evaporate in sunlight)),, redred ( (granules center left, chunk granules center left, chunk center rightcenter right), ), violetviolet ((produced by day-long annealing of red phosphorus above 550 °Cproduced by day-long annealing of red phosphorus above 550 °C) ) and and blackblack ( (== heating white phosphorus under high pressures 12,000 standard heating white phosphorus under high pressures 12,000 standard atmospheresatmospheres) )

phosphorus phosphorus Must be kept under water in pure formMust be kept under water in pure form Very poisonous 50mg fatal dose (white form)Very poisonous 50mg fatal dose (white form) Obtained from phosphate rock (apatite, Ca3(PO4)2 ) found in China,Obtained from phosphate rock (apatite, Ca3(PO4)2 ) found in China, Russia, Morocco, Fl, TN, UT, IDRussia, Morocco, Fl, TN, UT, ID

At current At current consumption consumption ratesrates (fertilizers, (fertilizers, detergents, , pesticides, , nerve agents, , matches)), reserves will be depleted , reserves will be depleted in the next 50 to 100 yearsin the next 50 to 100 years

Phosphorus is the sixth most abundant element in living organisms. Phosphorus is the sixth most abundant element in living organisms. Is found in every cell (Phosphate)!!Is found in every cell (Phosphate)!! Phosphate chemical reactions in in the the living cellsliving cells: : ≈≈ 23712371

red (granules center left, chunk center right)waxy white (yellow cut) black

Η φιλοσοφική λίθος και ο Η φιλοσοφική λίθος και ο φωσφόροςφωσφόρος

The 'squared circle' or The 'squared circle' or 'squaring the circle' is a 17th 'squaring the circle' is a 17th century alchemical glyph or century alchemical glyph or symbol for the creation of the symbol for the creation of the Philosopher's Stone. The Philosopher's Stone. The Philosopher's Stone was Philosopher's Stone was supposed to be able to supposed to be able to transmute base metals into transmute base metals into gold and perhaps be an elixir gold and perhaps be an elixir of lifeof life

Phosphorus - Phosphorus - Alchemical SymbolsAlchemical Symbols

"The Alchymist, In Search of the "The Alchymist, In Search of the Philosopher's Stone" painted by Joseph Philosopher's Stone" painted by Joseph

Wright in 1717 Wright in 1717 Hennig Brand in HamburgHennig Brand in Hamburg discovers phosphorus in discovers phosphorus in

16691669 from his urinefrom his urine. . He called the substance he had He called the substance he had discovered "cold fire" because it was discovered "cold fire" because it was luminous, glowing in the dark. luminous, glowing in the dark. White White phosphorus's natural phosphorus's natural chemiluminescence produces a chemiluminescence produces a rather dim green glowrather dim green glow

Brand sold his method to Johann Daniel Brand sold his method to Johann Daniel Kraft and Kunckel von Lowenstern Kraft and Kunckel von Lowenstern from from DresdenDresden for for 200 thaler200 thaler (=4191 $) (=4191 $)

For further payment he also revealed his For further payment he also revealed his secret to Gottfried Wilhelm Leibniz (Mr secret to Gottfried Wilhelm Leibniz (Mr calculus!!) calculus!!)

Leibniz, also thinking as an alchemist, Leibniz, also thinking as an alchemist, mistakenly believed Brand might be able mistakenly believed Brand might be able to discover the philosophers' stone by to discover the philosophers' stone by producing a large quantity of phophorus producing a large quantity of phophorus

Allies used phosphorusAllies used phosphorus incendiary incendiary bombs in World War IIbombs in World War II to destroy to destroy Hamburg, the place where the Hamburg, the place where the "miraculous bearer of light" was first "miraculous bearer of light" was first discovereddiscovered

Evelyn de Morgan: Greek gods Evelyn de Morgan: Greek gods PhosphorusPhosphorus and and Hesperus Hesperus --Πούλια Πούλια

& Αυγερινός& Αυγερινός Phosphorus Phosphorus ((gr.gr. Eosphoros, Eosphoros, l. l. Lucifer) and Lucifer) and HesperusHesperus((gr.gr. Hesperos, Hesperos, l. l. Vesper) are brothers, Vesper) are brothers, sons of the rosy fingered goddess of dawn, sons of the rosy fingered goddess of dawn, EosEos (latin: Aurora). (latin: Aurora).

PhosphorusPhosphorus is the planet Venus when it appears as the is the planet Venus when it appears as the morning star (morning star (ΑυγερινόςΑυγερινός). ). Hesperus (Hesperus (ΑποσπερίτηςΑποσπερίτης) is the ) is the planet Venus when it appears as the evening star. The planet Venus when it appears as the evening star. The early greeks believed these to be two distinct early greeks believed these to be two distinct astronomical bodies and assigned two distinct dieties to astronomical bodies and assigned two distinct dieties to the planet as it appeared respectively in the morning and the planet as it appeared respectively in the morning and evening. The later greeks adopted the Babylonian view evening. The later greeks adopted the Babylonian view that the morning and evening star were a that the morning and evening star were a single wandering star and associated it with the goddess single wandering star and associated it with the goddess AphroditeAphrodite((l.l. Venus). Venus).

Like the goddess Like the goddess VenusVenus and the stars and the stars themselves,  themselves,  PhosphorusPhosphorus and and HesperusHesperus are are eternally young and beautiful. eternally young and beautiful.

Only their mother Only their mother Eos Eos (Dawn) and her sister and (Dawn) and her sister and brother, brother, Selene Selene (the moon) and (the moon) and HeliosHelios(the Sun), shine (the Sun), shine more brightly in the heavens.more brightly in the heavens.

It is It is PhosphorusPhosphorus, the bringer of light, who wakes , the bringer of light, who wakes his mother his mother EosEos from her sleep in the depths of from her sleep in the depths of the sea each morning and ushers in the dawn. It the sea each morning and ushers in the dawn. It is is HesperusHesperus who ushers in the evening at dusk. who ushers in the evening at dusk. HesperusHesperus brings all good things home at the end  brings all good things home at the end of the day. He is the god of the hearth and of the day. He is the god of the hearth and domestic happiness. domestic happiness.

One might curse One might curse PhosphorusPhosphorus when getting up in the when getting up in the morning to go to work and bless morning to go to work and bless HesperusHesperus in the evening in the evening when returning to the comfort of home. when returning to the comfort of home.

Παραγωγή Φωσφόρου Παραγωγή Φωσφόρου κατάκατά Brand Brand

EvaporateEvaporate human urine human urine black black residueresidueleave it for a few monthsleave it for a few months

Then heat the residue with sandThen heat the residue with sand condense the variety of gases and oils, condense the variety of gases and oils, driving off in waterdriving off in water

The final substance to be driven off, The final substance to be driven off, condensing as a white solid, is condensing as a white solid, is phosphorus !!!phosphorus !!!

Παραγωγή: 1100 Παραγωγή: 1100 L L ούρωνούρων (60 κουβάδες (60 κουβάδες αλχημιστικά ούρα !!) αλχημιστικά ούρα !!) 60 gr 60 gr

???????????????

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 85% of P in body ) Structure of cell membranes Energy storage and

metabolism

Genetic translation (DNA) and DNA) and protein synthesis (RNA)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)

Form Function

P is essential element for P is essential element for metabolic processesmetabolic processes

ATPATP +ADP= +ADP= remains fairly remains fairly constantconstantThe human body total quantity:

0.1 mole (about 6 x 1022 molecules). Human cells require the hydrolysis of 100 to 150 moles (6 to 9 x 1025 molecules) of ATP daily (50-75 kg/day).

ATP molecule is recycled 1000 to 1500 times daily, or about once every minute

ATP + ADP constant

ATP + H2O → ADP + Pi   ΔG˚ = −30.5 kJ/mol (−7.3 kcal/mol) ATP + H2O → AMP + PPi   ΔG˚ = −45.6 kJ/mol (−10.9 kcal/mol)

Molecular formula C10H16N5O13P3

Molar mass 507.18 g mol−1

80kg 72yrs BMR Harris Benedict = 1644 kcal75kg=147.89 x 10.9=1611.65

PhosphorylationPhosphorylation- - PhotophosphorylationPhotophosphorylation

The addition of a The addition of a phosphate (PO (PO44) group to another ) group to another molecule, including any molecule, including any protein, is phosphorylation. , is phosphorylation. Many Many enzymes and and receptors are switched "on" or are switched "on" or "off" by phosphorylation. Phosphorylation is catalyzed "off" by phosphorylation. Phosphorylation is catalyzed by specific by specific protein kinases. . Phosphorylation of any Phosphorylation of any amino acid having a free having a free hydroxyl

group on a given protein can change the function, on a given protein can change the function, association, or localization of that protein.association, or localization of that protein.

Dephosphorylation is catalyzed by Dephosphorylation is catalyzed by phosphatases. .

Oxidative phosphorylation is the process of oxidizing is the process of oxidizing nutrients to produce to produce adenosine triphosphate (ATP). (ATP). Substrate-level phosphorylation forms ATP forms ATP by the direct transfer of a phosphate group to by the direct transfer of a phosphate group to adenosine diphosphate (ADP) (ADP) from a from a reactive intermediate. . Photophosphorylation uses solar energy to synthesize ATP. uses solar energy to synthesize ATP.

Phosphorylation of Phosphorylation of sugars allows cells to accumulate allows cells to accumulate sugars because the phosphate group prevents the sugars because the phosphate group prevents the molecules from diffusing back across their molecules from diffusing back across their transporter.transporter.

Phosphate reservesPhosphate reserves

A well-fed adult in the industrialized world A well-fed adult in the industrialized world consumes and excretesconsumes and excretes:: 1-3 g of phosphorus per day in the form of phosphate 1-3 g of phosphorus per day in the form of phosphate

(2-6 x 10(2-6 x 102222 molecules). molecules). PPhosphorus hosphorus in a in a "standard man" of 70 kg "standard man" of 70 kg :: 780 g780 g

or 1.1% (as 1.52 x 10or 1.1% (as 1.52 x 102525 molecules of phosphate molecules of phosphate)) 1.4 g/kg1.4 g/kg (98 g, 1.9 x 10 (98 g, 1.9 x 102424 molecules of phosphate) are molecules of phosphate) are

present in soft tissuepresent in soft tissue 675 gr675 gr (1.33 x 10 (1.33 x 102525 molecules of phosphate) in molecules of phosphate) in

mineralized tissue such as bone and teeth such as bone and teeth 0.1%0.1% of body phosphate (about 2 x 10 of body phosphate (about 2 x 102222 molecules) molecules)

circulates in the bloodcirculates in the blood this amount reflects the amount of phosphate available to soft this amount reflects the amount of phosphate available to soft

tissue cellstissue cells Blood plasma contains orthophosphate (as Blood plasma contains orthophosphate (as

HPOHPO442-2-) and H) and H22POPO44

-- in the ratio of about 4:1. in the ratio of about 4:1.

POPO443–3– :: molar mass= molar mass= 94.97 g/mol94.97 g/mol

0-phosphate-3D-balls.pngIn strongly basic conditions

1-hydrogenphosphate-3D-balls.png In weakly basic conditions

2-dihydrogenphosphate-3D-balls.png In weakly acid conditions

phosphoric-acid-3D-balls.png In strongly acidic conditions

Πάρτε μια αγελάδαΠάρτε μια αγελάδα

About 1,000,000 tones of elemental phosphorus is produced About 1,000,000 tones of elemental phosphorus is produced annually.annually.

In 2000, the global population produced 3 million tones of In 2000, the global population produced 3 million tones of phosphorus from urine and faeces alone !!!!!. phosphorus from urine and faeces alone !!!!!.

Phosphorus-Phosphates: Phosphorus-Phosphates: Normal serum levelsNormal 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:Alternative Names: Phosphorus - serum; HPO4-2, PO4-3; Inorganic phosphate; Phosphorus Phosphorus - serum; HPO4-2, PO4-3; Inorganic phosphate; Phosphorus blood test blood test

The serum concentration of phosphate may not reflect true phosphate stores.The serum concentration of phosphate may not reflect true phosphate stores. VARIES significantly with age!!!VARIES significantly with age!!!

Mammaliam cell internal phosphate levelsMammaliam cell internal phosphate levels= = 75 75 mEq/L. mEq/L. ISF ISF ==44 mEq/L mEq/L

AGE PHOSPHORUS

0–5 day 4.8–8.2 mg/dL

1–3 yr 3.8–6.5 mg/dL

4–11 yr 3.7–5.6 mg/dL

12–15 yr 2.9–5.4 mg/dL

16–19 yr 2.7–4.7 mg/dL

Phosphate metabolism and causes of hypophosphatemia

Geerse et al. Critical Care 2010, 14:R147Gaasbeek A, Meinders AE. Hypophosphatemia: An update on its etiology and treatmentThe American Journal of Medicine 2005; 118: 1094-1101 LIAMIS G, MILIONIS H, ELISAF M. Medication-induced hypophosphatemia: a review. Q J Med 2010; 103:449–459

PTH =↓ renal resorption of phosCalcitriol (1,25 Vit D) ↑ intestinal absorption of phos and helps renal resorption of phos.Absorption of phosphate can be blocked by aluminum-, calcium-, and magnesium-containing antacids..

Dietary P is absorbed in small intestine, excess is excreted by kidneys

Prevalence and/or incidence of hypophosphatemia

Geerse et al. Critical Care 2010, 14:R147

Up to 5% of hospitalized pts may have S. PO4 less than 2.5mg%.In alcoholics, 30-50% have been reported.

Reported incidence of hypophosphatemia

Gaasbeek A, Meinders AE. Hypophosphatemia: An update on its etiology and treatmentThe American Journal of Medicine 2005; 118: 1094-1101

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.

Κλινικές εκδηλώσεις Κλινικές εκδηλώσεις

Geerse et al. Critical Care 2010, 14:R147

Gaasbeek A, Meinders AE. Hypophosphatemia: An update on its etiology and treatmentThe American Journal of Medicine 2005; 118: 1094-1101

TreatmentTreatment Intravenous therapy (severe deficiency or cannot tolerate Intravenous therapy (severe deficiency or cannot tolerate

oral)oral) Sodium phosphate or potassium phosphateSodium phosphate or potassium phosphate Choice based on K+ level Choice based on K+ level Starting doses are 0.08–0.16 mmol/kg over 6 hr. Starting doses are 0.08–0.16 mmol/kg over 6 hr.

The oral preparations of phosphorus are available with The oral preparations of phosphorus are available with various ratios of sodium and potassium. Oral maintenance various ratios of sodium and potassium. Oral maintenance doses are 2–3 mmol/kg/day in divided doses. (cause doses are 2–3 mmol/kg/day in divided doses. (cause diarrhea)diarrhea)

Increasing dietary phosphorus is the only intervention Increasing dietary phosphorus is the only intervention needed in infants with inadequate intake. needed in infants with inadequate intake.

Certain diseases require specific therapy. Certain diseases require specific therapy. Nutritional vitamin D deficiency Nutritional vitamin D deficiency

Vitamin D supplementation, not phosphorus, is the principal Vitamin D supplementation, not phosphorus, is the principal therapy therapy

X-linked hypophosphatemic rickets X-linked hypophosphatemic rickets Combination of 1,25-dihydroxyvitamin D and oral phosphorus.Combination of 1,25-dihydroxyvitamin D and oral phosphorus.

Intravenous treatment of hypophosphatemia

Geerse et al. Critical Care 2010, 14:R147

CRRT : CRRT : PhosphatePhosphate and and MagnesiumMagnesium

HypophosphatemiaHypophosphatemia and and HypoHypomagnesiemia magnesiemia occur in almost occur in almost all patients on CRRT for ≥ 48 hours.all patients on CRRT for ≥ 48 hours.

Management:Management: Routinely supplement patients with IV Routinely supplement patients with IV

PO4 and MgSO4 on regular basis:PO4 and MgSO4 on regular basis: Sodium phosphate 20 mmol in 250 mls IV Sodium phosphate 20 mmol in 250 mls IV

fluid over 3-4 hours q 8-12 hoursfluid over 3-4 hours q 8-12 hours Magnesium sulphate 2 gm IV q 8-12 H, Magnesium sulphate 2 gm IV q 8-12 H,

Average daily intake of phosphorous = 1000mg

Approximately 50% absorbed = 500mg

Dialysis removes around 300mg

Daily net positive balance = +200mg

Therefore oral phosphate binders needed to reducephosphate absorption by at least 200mg

Phosphate Control Phosphate Control in ESRDin ESRD

Practice Case 1Practice Case 1

A 15-year-old girl is admitted to your facility with A 15-year-old girl is admitted to your facility with severe anorexia nervosa and amenorrhea. She severe anorexia nervosa and amenorrhea. She weighs 35 kg and is 160 cm tall. She has bradycardia weighs 35 kg and is 160 cm tall. She has bradycardia and orthostatic hypotension. You plan to stabilize and orthostatic hypotension. You plan to stabilize her medically and begin nasogastric tube feeding.her medically and begin nasogastric tube feeding.

Of the following, the electrolyte abnormality that is Of the following, the electrolyte abnormality that is MOST likely to occur during the first week of her MOST likely to occur during the first week of her treatment istreatment is

A. hypercalcemiaA. hypercalcemiaB. hyperphosphatemiaB. hyperphosphatemiaC. hypocalcemiaC. hypocalcemiaD. hyponatremiaD. hyponatremiaE. hypophosphatemiaE. hypophosphatemia

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 2Practice Case 2

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

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)

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

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

67 yrs ♀. Προηγούμενο ιστορικό: Παχυσαρκία, Κύφωση, Κάπνισμα (½

πακ/ημέρα), άπνοια του ύπνου, υπέρταση (micardis 1/2x1), ΧΑΠ, ΣΔ ( glucophage 1x2, solosa 1x1), ΝΦΔ ( xanax 0,25x2)

Προγραμματισμένη επέμβαση για κοιλιοκοίλη (29/6/11) σε ιδιωτική κλινική μεταφορά σε ΜΑΦ λόγω ΜΤΧ ΟΑΑ (υποξαιμία) διασωλήνωση – εισαγωγή σε ΜΕΘ (1/7/11) μεταφορά στην ΠΑΝ ΜΕΘ (4/7/11) GCS 11T, καταστολή, εμπύρετος 38ο C Αιμοδυναμική αστάθεια υπό νοραδρεναλίνη 15 γ/λεπτό ΗΚΓ- φλεβόκομβος, RBBB Αναπνευστική ανεπάρκεια υπό ΜΥΑ, FiO2 0.9-1.0, PEEP 10 Βρογχόσπασμος, μείωση αναπν. ψιθυρίσματος αριστερά Α/Α θώρακος - πυκνοατελεκτασία αριστερά Διούρηση μειωμένη υπό lasix Κοιλία – εντερικοί ήχοι υπάρχουν, φέρει 2 παροχετεύσεις

Διακομιδή από ιδιωτική κλινική 4 ημέρες μετά από Προγραμματισμένη επέμβαση για κοιλιοκοίλη (29/6/11), για αναπνευστική ανεπάρκεια/λοίμωξη του αναπνευστικού/σηπτικό shock.

Practice Case 3Practice Case 3

77 ημέρες στη ΜΕΘΣηπτικό shock

34/77 (44.1 %) ημέρες: Φυσιολογικός φωσφόρος 6/77 (7.8 %) ημέρες: Υπεφωσφαταιμία 27/77 (35.1 %) ημέρες: Υποφωσφαταιμία 10/77 (12,9%) ημέρες: Δεν μετρήθηκε

0

2

4

6

8

10

12

04.07

.11

10.07

.11

15.07

.11

20.07

.11

23.07

.11

27.07

.11

01.08

.11

06.08

.11

09.08

.11

12.08

.11

15.08

.11

18.08

.11

21.8.

11

24.8.

11

27.81

1

30.8.

11

2.9.

11

5.9.

11

8.9.

11

11.9.

11

14.9.

11

17.9.

11

Ca

PO43

Mg

CREATININE

CVVHDF

Νέο Σηπτικό shock

Νέο Σηπτικό shock

MSOF

Glucophos 20-40mmol

3Τ

11Τ

Μερικοί χρήσιμοι υπολογισμοί

Calculation: FE PO4=(U PO4 * Pcr) * 100/ P PO4* Ucr

Με δικη της διούρηση 351 mg Fractional Excretion of PO4(FENa) = (1.3PCr * 0.9 U PO4 ) / (3.5P PO4 x 4.6UCr) %=7.26%

Με φίλτρο 1347.34 mgFractional Excretion of PO4 (FEPO4) = (0.7PCr * 2.8U PO4 ) /(3P PO4 x 0.4UCr) %=163,33%

PCr (mg%) UPO4 (mg%) UCr (mg%) PPO4 (mg%)CVVHDF 0.7 2.8 0.4 3

Λειτουργία Νεφρών 1.3 0.9 4.6 3.5

HyperphosphatemiaHyperphosphatemia::Clinical ManifestationsClinical Manifestations

Hypocalcemia Hypocalcemia Tissue deposition of calcium-phosphorus saltTissue deposition of calcium-phosphorus salt Inhibition of 1,25-dihydroxyvitamin D productionInhibition of 1,25-dihydroxyvitamin D production Decreased bone resorption. Decreased bone resorption.

Symptomatic hypocalcemia is most likely when Symptomatic hypocalcemia is most likely when phosphorus increases rapidly phosphorus increases rapidly diseases predisposing to hypocalcemia are present diseases predisposing to hypocalcemia are present

chronic renal failurechronic renal failure rhabdomyolysis). rhabdomyolysis).

Systemic calcificationSystemic calcification Solubility of phosphorus and calcium in the plasma is Solubility of phosphorus and calcium in the plasma is

exceeded. exceeded. Inflamed conjunctiva- foreign body feeling, erythema, and Inflamed conjunctiva- foreign body feeling, erythema, and

injection. (BOBBY) injection. (BOBBY) Hypoxia from pulmonary calcificationHypoxia from pulmonary calcification Renal failure from nephrocalcinosis.Renal failure from nephrocalcinosis.

Diagnostic TestingDiagnostic Testing Assess renal function: Bun and creatinine. Assess renal function: Bun and creatinine. Focus history on intake of phosphorus and Focus history on intake of phosphorus and

the presence of chronic disease. the presence of chronic disease. If suspect rhabdomyolysis, tumor lysis, or If suspect rhabdomyolysis, tumor lysis, or

hemolysishemolysis Check potassium, uric acid, calcium, LDH, Check potassium, uric acid, calcium, LDH,

bilirubin, and CPK bilirubin, and CPK If mild hyperphosphatemia and sign If mild hyperphosphatemia and sign

hypocalcemia hypocalcemia check serum PTH level check serum PTH level

Distinguishes between hypoparathyroidism and Distinguishes between hypoparathyroidism and pseudohypoparathyroidism.pseudohypoparathyroidism.

TreatmentTreatmentDepends on its severity and etiology. Depends on its severity and etiology. Dietary phosphorus restriction- in mild hyperphosphatemia Dietary phosphorus restriction- in mild hyperphosphatemia Intravenous fluids- enhance renal excretion if kidney Intravenous fluids- enhance renal excretion if kidney

function is intact. function is intact. Oral phosphorus binder- in significant hyperphosphatemia Oral phosphorus binder- in significant hyperphosphatemia

Prevents absorption of dietary phos Prevents absorption of dietary phos Removes phos from the body by binding what is normally secreted Removes phos from the body by binding what is normally secreted

and absorbed by GI tract and absorbed by GI tract Binders containing aluminum hydroxide or use calcium carbonate if Binders containing aluminum hydroxide or use calcium carbonate if

also hypocalcemic. also hypocalcemic. Aluminum-containing binders NOT used in CRF because of aluminum toxicity. Aluminum-containing binders NOT used in CRF because of aluminum toxicity. Esp if taking oral citrate, which ↑ gastrointestinal absorption of aluminum.Esp if taking oral citrate, which ↑ gastrointestinal absorption of aluminum.

Preservation of renal function-high urine flow permits Preservation of renal function-high urine flow permits continued excretion continued excretion

Dialysis directly removes phosphorus from the blood in Dialysis directly removes phosphorus from the blood in ESRD ESRD only an adjunct to dietary restriction and phosphorus binders only an adjunct to dietary restriction and phosphorus binders dialysis is not efficient enough to keep up with normal dietary intake.dialysis is not efficient enough to keep up with normal dietary intake.

Phosphate removal by dialysis – difficult!Phosphate removal by dialysis – difficult!

• Phosphate is mostly found intracellularlyPhosphate is mostly found intracellularly

• Has a large sphere of hydrationHas a large sphere of hydration

• Cleared rapidly from serum in first 2 hours of HDCleared rapidly from serum in first 2 hours of HD

• Rebounds significantly at 3 - 4 hours post – HDRebounds significantly at 3 - 4 hours post – HD

• Consequently slightly better clearance by PDConsequently slightly better clearance by PD

• Excellent clearance by daily home HDExcellent clearance by daily home HD

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