Similarities between Potassium and Phosphorus

Transcription

1 Disturbnces of the Potssium nd Phosphorus Metbolism in Periprturient Diry Cows Wlter Grünberg Similrities between Potssium nd Phosphorus Predominntly intrcellulr electrolytes Blnce strongly dependent on orl intke Importnt losses through the mmmry glnd Both ssocited with muscle function Disturbnces of the electrolyte blnce re common in periprturient diry cows 1

2 Dissimilrities No storge form of potssium vilble in the body Lrge reserves of phosphorus in bone Tight regultion of extrcellulr potssium concentrtion Plsm [Pi] not tightly regulted Regultion of potssium homeostsis resonbly well understood Poor understnding of mechnisms regulting the P homeostsis Symptoms of cute disturbnces of the (extrcellulr) potssium homeostsis well defined Relevnce of hypophosphtemi controversilly debted Potssium nd Phosphte in Blood Periprturient Period Helthy Cow Plsm Potssium Plsm Phosphte 4,8 3,0 4,6 4,4 2,5 Plsm [K] (mmol/l) 4,2 4,0 3,8 3,6 Plsm [Pi] (mmol/l) 2,0 1,5 1,0 3,4 3,2 0,5 3, Time reltive to clving Zeit (Tge reltiv zur Klbung) 0, Time Zeit (Tge reltive zur to clving Klbung) Grünberg et l

3 Potssium nd Phosphte in Blood Periprturient Period Sick Cow Left displced bomsum Plsm [Pi] norml 57 % decresed 35 % incresed 8 % Plsm [K] norml 45 % decresed 55 % incresed <1 % Grünberg et l Constble et l Plsm [K] (mmol/l) Serum [K] (mmol/l) Potssium nd Phosphte in Blood Periprturient Period Sick Cow LMV - LDA links Constble et l LMV - rechts Plsm [Pi] (mmol/l) Serum [Pi] (mmol/l) Serum [Pi] in cows with LDA nd RDA /AV n= 1189 n= 179 LMV-links LMV-links AV LMV- LDAlinks RDA / AV Grünberg et mmol/l l m 3

4 Relevnce of Disturbed Electrolyte Blnce in Periprturient Cows Hypoklemi Membrne potentil disturbnces of excitble cells Altered function of strited nd smooth muscles Altered crdic function Extrcellulr [K] sustined t expense of intrcellulr K? Hypophosphtemi Relevnce uncertin Intrcellulr P blnce is presumbly more relevnt Intrcellulr P sustined t expense of extrcellulr P? Potssium Homeorrhesis in Erly Lcttion Ttrockenmsseufnhme (kg/24h) Zeit reltiv zur Geburt (Tge) Feed intke t it s ndir round prturition Sudden onset of K losses through milk fter prturition Grünberg et l K (mmol/dy) Sfwte et l

5 Regultion of the Extrcellulr Potssium Blnce Counterregultion to hyperklemi Comprtmentl shift of K into the cell Renl excretion Intestinl excretion Counterregultion to hypoklemi Shift of K from intrcellulr to extrcellulr spce Less efficient with less muscle mss Renl retention of K Requires wter nd N excretion Reduced [K] in milk Hypoklemi in Sick Cows Etiology not entirely understood Decresed feed intke Delyed gstrointestinl trnsit time Alklosis Dehydrtion (Aldosterone)? Itrogenic (glucose, rehydrtion, glucocorticoids ) 5

6 Itrogenic Excerbtion of Hypoklemi Prenterl Dextrose Infusion Prenterl Hypertonic NCl Expect decline > 0.8 mmol/l with stndrd tretment Administrtion of NHCO 3 Lrge volumes of fluid Corticoids. Plsm [K] (mmol/l) 4,0 3,8 3,6 3,4 3,2 3,0 2,8 Glukose Klium Zeit nch Glukoseinfusion (h) Plsm [Glukose] (mmol/l) Clinicl Implictions of Hypoklemi 6

7 Hypoklemic Recumbency Clinicl presenttion differs from milk fever Resembling botulism Decresed tone of tongue- nd hed / neck muscles Rubber neck / hed on the ground Pronounced hypoklemi [K] < 2.0 mmol/l Frequently ssocited with crdic rrhythmi Atril fibrilltion Subclinicl Implictions of Hypoklemi Hypoklemi nd Abomsl Motility Turck & Leonhrd-Mrek

8 Potentil Clinicl Implictions of Hypoklemi Decresed Resting-Membrne Potentil of Excitble Cells mv 0 Restingpotentil Triggerpotentil Normoklemi Hypoklemi Potssium s C-Antgonist with Hyperclcemi mv Trigger potentil -90 Resting potentil Hyperclcemi Hypoclcemi Normoklemi

9 Potssium s C-Antgonist with Hyperclcemi mv Incresed risk of complictions fter IV clcium in hypoklemic cows?? 0-30 Triggerpotentil -60 Hyperclcemi -90 Resting potentil Normoklemi Hypoklemi -120 Plsm Phosphte (Pi) in Helthy Periprturient Diry Cows Clving 2,5 Plsm Clcium Plsm [Pi] (mmol/l) 2,0 1,5 1,0 0,5 Plsm Clcium (mmol/l) 3,0 2,8 2,6 2,4 2,2 2,0 1,8 1,6 1, Dys reltive to clving (=0) 0, Tge (reltiv zur Klbung Dys reltive = 0) to clving Dys reltive to clving Grünberg et l

10 Mechnisms Presumed behind Periprturient Hypophosphtemi Loss of P through udder Decresed feed intke Decresed GI motility Hormonl dpttion PTH Cortisol Lg time of counter regultion Plsm Clcium nd Phosphte t the Onset of Lcttion Clcium Mstectomized cows Phosphte Intct cows Goff et l

11 Plsm Phosphte nd Cortisol Kim et l Plsm Phosphte nd Cortisol Kim et l

12 Incidence of Periprturient Hypophosphtemi Metbolic Profiling of Cliniclly Helthy Diry Cows 54% on the dy of clving Stufenbiel 2002 Over 15% in the first 10 dys of lcttion 10% between 10 nd 20 dys of lcttion Mcre et l Mcre et l Incidence of Periprturient Hypophosphtemi Metbolic Profiling of Cliniclly Helthy Diry Cows 54% on the dy of clving Stufenbiel 2002 Over 15% in the first 10 dys of lcttion 10% between 10 nd 20 dys of lcttion Mcre et l Mcre et l

13 Incidence of Hypophosphtemi in Recumbent Periprturient Diry Cows Electrolyte sttus Study C P Bostedt et l Bostedt et l Stoll 2000 Metzner nd Klee 2005 [C] [Pi] 60,2% 67,5% 64,4% 62,4 [C] [Pi] 10,8% 12,1% 1,0% 4,1% [C] [Pi] 18,2% 13,7% 28,7% 18,4% [C] [Pi] 10,8% 6,7% 5,9% 15,1% Incidence of Hypophosphtemi in Recumbent Periprturient Diry Cows Electrolyte sttus Study C P Bostedt et l Bostedt et l Stoll 2000 Metzner nd Klee 2005 [C] [Pi] 60,2% 67,5% 64,4% 62,4 [C] [Pi] 10,8% 12,1% 1,0% 4,1% [C] [Pi] 18,2% 13,7% 28,7% 18,4% [C] [Pi] 10,8% 6,7% 5,9% 15,1% 13

14 Hypophosphtemi nd Periprturient Recumbency PR= Positive responders ADC= Alert Downer Cows Ménrd nd Thompson 2007 Wht Hppens if Diry Cows re Trnsiently P-Deprived? Some experimentl results of the pst yers. 14

15 Wht Hppens if Diry Cows re Trnsiently P-Deprived? Mke the difference between trnsient (cute) nd chronic phosphte deficiency Chronic Dietry P-Deprivtion 80 Averge feed intke for cows fed different dietry P concentrtions 700 Averge body weight of cows fed different dietry P concentrtions Feed intke (MCl digest. energy /dy) % % dietry P of DM P 0.32% % dietry P of DM P 0.42% % dietry P of DM P Body weight (kg) % 0.24 % dietry P of DM P 0.32% 0.32 % dietry P of DM P 0.42% % dietry P of DM P Week of lcttion Cll et l Week of lcttion 15

16 Chronic Dietry P-Deprivtion 35 Averge Milk Yield for Cows fed different dietry P concentrtions Feed intke (MCl digest. energy /dy) Averge feed intke for cows fed 15 different dietry P concentrtions 0.24% % dietry P of DM P 0.32% % dietry P of DM P 0.42% % dietry P of DM P Milk yield (kg/d) % 0.24 % dietry P of PDM 0.32% % dietry P of PDM 0.42% % dietry P of PDM Body weight (kg) Week of lcttion Averge body weight of cows fed different dietry P concentrtions 0.24% 0.24 % dietry P of DM P 0.32% 0.32 % dietry P of DM P 0.42% 0.42 % dietry P of DM P Week of lcttion Cll et l Week of lcttion Recommendtion Stndrds for Dietry P in the Industrilized World Lcttion UK D USA NL Milk (kg/d) DMI (kg/d) g P/d % DM g P/d % DM g P/d % DM g P/d % DM , , , , ,3 77 0, , , , ,6 99 0, , , , , , , , , , , , ,32 modified from Pfeffer et l

17 Phosphorus-Recommendtion Stndrds for Diry Cttle Dietry P-Gehlt P content der Rtion (% of (%) DM) Milk Milchleistung production (kg/d) P-Digestibility = 70 % Concerns with Trnsient P-Deficiency in Periprturient Cows Postprturient Hemoglobinuri Downer Cow Syndrome Disturbed liver function 17

18 Dietry P-Depletion of non-periprturient Diry Cows Pilot-Study on 10 pst-pek Diry Cows Fed P-deficient diet for 5 weeks Rtion with 0.18 % P in DM Then supplemented with P for 2 weeks Rtion with 0.47 % P/in DM Dietry P-Depletion of non-periprturient Diry Cows Acclimtiztion Acclimtion Depletion Repletion 2,5 d 2,0 Plsm [Pi] (mmol/l) 1,5 1,0 0,5 b b b b b bc bc c c c d d d 0, Dy Time of (dy study of study) Grünberg et l

19 No ltered demenor No clinicl disese Clinicl Signs No noticeble drop in feed intke or milk production DMI: 20.4 ± 2.5 kg DM/dy Milk: 23.6 ± 3.7 kg Milk/dy No signs of muscle wekness No signs of nemi or hemolysis Counterregultory Mechnisms Bone Mobiliztion Acclimtiztion Depletion Repletion Urine pyridinoline / Cre rtio (µg/g Cre) AC AC AB AB B B Pyridinoline / cre Desoxypyridinoline / cre AB B C C Urine desoxypyridinoline / cre rtio (µg/g Cre) Time (dy of study) Grünberg et l

20 Phosphorus in Muscle Tissue Muscle tissue P (mg/g wet weight) 2,0 1,8 1,6 1,4 1,2 1,0 Acclimtiztion Depletion Totl P Pi Time (dy of study) Repletion 1,3 1,2 1,1 1,0 0,9 0,8 0,7 0,6 Muscle tissue cid soluble Pi (mg/g wet weight) Grünberg et l Electromyogrphy No pprent signs of muscle wekness EMG-results did not suggest energy deficiency (ATP or cretine phosphte-depletion) Incresed occurrence of pthologic spontneous ctivity (PSA) in muscle fibers Suggestive membrne instbility or neuromyopthy Grünberg et l

21 Dietry P-Deprivtion in Trnsition Diry Cows Two groups Group C Group LP (low-phosphte) Study period from 6 weeks nteto 6 weeks post-prtum P-deficient diet for LP cows from 4 weeks.p. to 4 weeks p.p % P in DM nteprtum 0.20 % P in DM postprtum Dietry P-Deprivtion in Trnsition Diry Cows 2,5 Acclimtion Depletion Repletion 2,0 Plsm [Pi] (mmol/l) 1,5 1,0 0,5 Control LP 0, Dys Tge reltive to zur clving Geburt Grünberg et l

22 Clinicl Findings No bnorml demenor until prturition No disese occurrence No feed intke depression No signs of muscle wekness Periprturient period Control: 4 /18 Cows with clinicl hypoclcemi (stge I nd II) Group LP: Uneventful prturition, no clinicl hypoclcemi, no recumbencies Periprturient Clcium Blnce in P-deprived Diry Cows Control LP Dys reltive to clving Cohrs et l

23 Mechnisms of periprturient C-Mobilistion Bone Mobiliztion Despite of Blunted Increses in PTH Crosslps PTH Control LP Control LP 1,25-OHD Muscle Tissue Composition nd Function No clinicl signs of muscle function disturbnce P-deprivtion does not lter muscle tissue P, Pi, ATP, ADP, AMP or cretine phosphte content No biochemicl indiction of muscle cell dmge Incresed occurrence of pthologicl spontneous ctivity (PSA) in muscle fibers 23

24 Feed Intke nd Milk Production Feed Intke Milk Production kg TM/Tg Control LP Milk yield (kg/d) Milchleistung (kg/tg) Control LP Dys Tge reltive zur to Klbung clving Tge reltiv zur Klbung Dys reltive to clving Negtive Energy Blnce Plsm [NEFA] Plsm {NEFA] Liver Tricylgylcerol (TAG) Acclimtion Depletion Repletion Clving Control Plsm [NEFA] (µmol/l) Control LP Liver TAG content (mg/g wet weight) A A B b LP B b B Dys reltive to clving Woche reltiv zur Klbung Smpling time 24

25 Postprturient Hemoglobinuri 5/18 P depleted cows Alwys in 2. week of lcttion Durtion 3 5 dys Postprturient Hemoglobinuri Preliminry Conclusions Hemolysis occurred in nrrow time window reltive to clving Predisposition? P-Deprivtion seems to ply role Other fctors? Destruction of specific erythrocytes? Cnnot be controlled After lysis of specific erythrocytes, norml regenertive ctivity even during sustined P-deprivtion 25

26 Disturbnces of the Potssium nd Phosphorus Metbolism in Periprturient Diry Cows Synopsis Synopsis Homeostsis of phosphorus nd potssium re both chllenged in periprturient cows Even more so in cows with feed intke depression Homeosttic disturbnces my well be consequence rther thn cuse of primry problem Clinicl nd subclinicl effect of blnce disorders for these electrolytes re poorly defined 26

27 Synopsis For both electrolytes incresing the supply in lte gesttion to prevent deficiencies in erly lcttion IS NOT n option Supplying these minerls (cse by bse bsis) in cows off feed should be considered s supportive cre tretment Tretment Options For both minerls prenterl tretment is unsuitble for the field sitution Phosphorus No products contining PO 4 commercilly vilble Bolus IV-infusion of PO 4 -solutions short lived effect (nd off lbel) Potssium Bolus IV-infusion not n option Drip infusion requires constnt monitoring of plsm [K] Orl supplementtion of both minerls is sfe effective (reltively) inexpensive 27

28 Solubility of Vrious Phosphte Slts Phosphte slt Solubility in g/100 g H 2 0 t 25 C NH 2 PO 4 Monosodium phosphte 94.9 N 2 HPO 4 Disodium phosphte 11.8 CHPO 4 Diclcium phosphte C(H 2 PO 4 ) 2 Monoclcium phosphte 1.8 KH 2 PO 4 Monopotssium phosphte 25.0 K 2 HPO 4 Dipotssium phosphte MgHPO 4 Mgnesium phosphte 0,025 Orl Tretment of Hypophosphtemi C(H 2 PO 4 ) 2 NH 2 PO 4 KHPO 4 Plsm Plsm [Pi] Plsm [Pi] 3,0 b b 3,0 b b Plsm Pi concentrtion (mmol/l) 2,5 2,0 1,5 1,0 b b CRu NRu Plsm Pi concentrtion (mmol/l) 2,5 2,0 1,5 1,0 b b,b,b,b,b KRu NRu Time reltive to tretment (min) Hours post tretment Time reltive to tretment (min) Hours post tretment Idink nd Grünberg

29 Orl Tretment of Hypophosphtemi Plsm [Pi] (mg/dl) Plsm Pi concentrtion (mmol/l) 3, , , , ,0 0 b Monoclciumphosphte (C(H 2 PO 4 ) 2 ) b vs. Diclciumphosphte (CH 2 PO 4 ) b Plsm [Pi] b C(H2PO4)2 NH2PO4 CRu NRu 2 4 Time reltive to tretment (min) 12 Hours post tretment Plsm [Pi] (mmol/l) 3,0 2, ,0 1, ,0 0 NH2PO4 CH2PO4 NH2PO4 rumen Col 1 v s Pi Time reltive to (min) Hours post tretment Idink nd Grünberg 2014 Grünberg et l Orl Tretment of Hypophosphtemi NH 2 PO 4, N 2 HPO 4, MgHPO 4, nd Control Cohrs nd Grünberg

30 Orl Tretment of Hypophosphtemi Tretment recommendtion: g P orlly every 12-24h in the form of: NH 2 PO g (First choice) N 2 HPO g KH 2 PO g (with concomitnt hypoklemi) C(H 2 PO 4 ) g (less effective, but my provide C) CHPO g (unsuitble for rpid correction of hypophosphtemi) MgHPO g (unsuitble for rpid correction of hypophosphtemi) Orl Administrtion of Potssium Rpid onset (ruminl bsorption) Sfe to dose KCl s Bolus- or Drench Durtion of effect? Tretment intervl? Avoid mssive over dosge Hyperklemi Osmotic dirrhe Mucosl irrittion? 30

31 Orl KCl Recommended Dosge Recommendtions re mostly empiricl! Mild / moderte Hypoklemi: g/600 kg/ KCl Moderte / severe hypoklemi: g KCl / 600 kg Avoid single doses > 250 g KCl / 600 kg Tretment intervl: 8-12h? Orl KCl Py Attention to Difference between K nd KCl Approx. 50% of the mss of KCl is K! x g KCl x/2 g K Content of K on the lbel often given s mount K (NOT s KCl) To tret even mild hypoklemi drench powder needs to contin t lest 30 g K (or 60 g KCl) / dose 31

32 Orl Tretment with KCl 200 g of KCl s Drench Plsm Potssium Concentrtion 5,5 Plsm [K] (mmol/l) 5,0 4,5 4,0 Time vs K Feeding Feeding 3,5 Tretment 3, Time reltive to tretment (h) Grünberg unpublished Wlter.gruenberg@tiho-hnnover.de 32

33 Recommendtion Stndrds for Dietry P Dry Cow g/kg ( %) DM (US) g/kg ( %) DM (D) g/kg ( %)DM (NL) C:P rtio considered obsolete in bovine Avoid excess of P (> 4.2 g/kg DM in close-up) P below 2.0 g kg/dm is probbly deficient in the dry-cow rtion Dietry P-Deprivtion in Trnsition Diry Cows Dietry P-content Acclimtion (dry cow) 2,8 g P/kg DM both groups Dry cow-period (4-5 weeks) Group LP: 1,5g P/kg DM Group C: 2,8g P/kg DM Erly lcttion (4-5 weeks) Group LP: 2,0g P/kg DM Group C: 4,2g P/kg DM Repletion (2 weeks) 4,2g P/kg DM both groups 33