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1 BEC FEED SOLUTIONS NEW ZEALAND Ltd Proudly sponsor Dr Alessandro Mereu Yara Feed Phosphates July 2017 NZARN Meeting
2 Phosphorus metabolism in cattle: principles and interactions with Ca and Mg Dr. Alessandro Mereu
3 Summary The Phosphorus Challenge P cycle in the dairy cow Regulation of extracellular P cycle Interaction with Ca Interacion with Mg Dietary factors affecting P cycle Biomarkers of the P status in the dairy cow Take home messages
4 The Phosphorus Challenge Current P requirements (NRC) are expressed using a factorial approach. maintenance, growth, pregnancy and lactation However dynamics of rumen P degradation, P absorption in the intestine, P recycling with saliva, P retention in milk and P mobilization or deposition in soft tissues and bones need to be quantified. Dynamics model would be more useful to explain P use and requirements in dairy cows and should not be treated as separate topic but integrated with the representation of other factors such as rumen function, intestinal digestion, nutrient delivery to the cow, nutrient delivery and utilization by the udder and excretion with urine and faeces
5 Phosphorus Cycle in the Dairy Cow
6 P Cycle and Distribution in Dairy Cows FEED > 0.5 mmol/l Small Intestine Large Intestine Rumen 1-3 mmol/l 4 15 mmol/l 80 85% 99% 100 MMOL/l Goselink et al., 2015
7 Regulation of extracellular P cycle
8 Regulation of Extracellular P 1 2 Gastro intestinal absorption BLOOD AND BONE EXCHANGE ENDOCRINE REGULATION Parathyroid hormone (PTH) Active Vitamin D 3 (calcitriol) Phosphatonins (FGF23) 3 MILK RETENTION 4 SALIVA Hill et al., 2008 J. Dairy Sci. 91:
9 Endocrine Regulation Vitamin D 3 Synthesized in kidneys Inuced by hypophosphatemia, hypocalcemia and PTH Intestinal P absorption can be upregulated even independently by Vit. D3 Stimulate FGF23 secretion Phosphatonins FGF23, sfrp-4 Reduces P balance by: renal excretion D3 synthesis P intake FGF 23 Not directly affected by plasma P concentration Goselink et al., 2015 PTH Tightly regulated by extracellular calcium Hyperphosphatemia: PTH secretion Hypophosphatemia: PTH secretion; Bergwitz et al., 2011
10 Interaction with Mg Unpaired Mg absorbability might lead to milk fever: Magnesium is critical in the release of parathyroid hormone and in the synthesis of Vitamin D3. In hypomagnesaemic states, kidney, bones and gut transporters are less responsive to PTH (Goff 2000; Sampson et al. 1983). Contreras et al. (1982) and van de Braak et al. (1987b) both demonstrated poor calcium mobilisation in hypomagnesaemic cattle
11 Interaction with Mg Mg absorption take place in the rumen (Uribe, PhD thesis) Solubility is maximized at low ph (Grace et al., 1977; Hom & Smith, 1978; Dalley et ai., 1997). In order to maximize absorbabilty, Mg supplements must be highly soluble at ruminal ph
12 Magnesium Oxide MgO very variable in terms of composition and quality due to Production processes and the origin of the rock Particle size Temperature Solubility CO C 6-9% C 38-43% HEAT! MgCO 3 + = MgO High Costs
13 Interaction with Mg MgO-A µ MgO-B µ MgO-C µ Xin et al., 1989 Urine mg/mg creatinine Control MgO-A MgO-B MgO-C Ca 0.05 a 0.02 a 0.04 ab 0.07 c
14 Endocrine Regulation - Summary Calcitriol, PTH and phosphatonins are the main hormones regulating phosphorus and calcium metabolism Hypophosphatemia Calcitriol - PTH and FGF23 P absorption from the gut P excretion from kidneys Hyperphosphatemia Calcitriol - PTH and FGF23 P absorption from the gut P excretion from kidneys
15 Endocrine Regulation - Summary PTH increases mainly in case of hypocalcaemia PTH: Ca absorption from the gut; Ca and P bone resorption; P excretio from kidneys PTH synthesis is Mg dependant Mg is essential for PTH synthesys and thereby Ca absorption No available body reserves Absorbed in the rumen Solubility at rumen ph is fundamental Particle size Production process
16 1 - Gastrointestinal Absorption of P P ABSORPTION Mostly absorbed in the small intestine Passive transport only at high dietary concentration Active transport mediated by NaP I co-transporters P and Ca absorption decoupled Foote et al., 2011 J. Dairy Sci. 94 : PTH (pmol/l) Calcitriol (pmol/l) Trt g/kg DM High P 4.6 Low P 2.0 High Ca 10.9 Low Ca High P High Ca Low P High Ca PTH (pmol/l) Calcitriol (pmol/l) High P Low Ca Low P Low Ca Pfeffer et al., Retained P (g/d) Retained Ca (g/d) Plasma P (mmol/l) Plasma Ca (mmol/l) 0 Retained P (g/d) Retained Ca (g/d) Plasma P (mmol/l) Plasma Ca (mmol/l)
17 2 - Blood and Bone Exchange Lactation stage Negative P Balance from the end of the dry period up to 4-5 weeks of lactation: Reduction of feed intake, high P requirment (milk and colostrum) High Ca requirements trigger release of PTH and Vitamin D activation stimulationg bone resorption and release of Ca and P Salazar et al., 2012
18 2 - Blood and Bone Exchange Pregnancy Bone metabolism is activated by pregnancy ( calcitriol, PTHrP in mammary gland and placenta) Dietary factors Hypocalcaemia promotes hypophosphatemia through PTH release (PTH increases Ca resorption from bones but contemporary increase P excretion from urines and excretion in saliva) Goselink et al., 2015
19 3 Milk Retention P EFFICIENCY = P intake (P in milk + P growth) / P intake Current requirements: g P/kg Milk (NRC, 2001, COMV 2005) Klop et al., 2014 Pfeffer et al., 2005 In milk about 70% of P inorganic Most of this P is in casein and lactose P affect not only production but also mik quality
20 4 - Saliva P regulation in saliva Salivary gland actively concentrate plasma P up to 4 15 mmol/l The mechanism ensure an adequate concentration of P in the rumen to optimize bacterial growth FEED Rumen Small Intestine Large Intestine Good rumination is thereby relevant to maintain optimal P levels in the rumen 1-3 mmol/l Increased PTH levels (hypocalcemia) stimulates P excretion in saliva and the decrase of bicarbonate 4 15 mmol/l 80 85% Goselink et al., 2015
21 Dietary Factors Affecting P Cycle
22 Dietary Factors Affecting P Cycle Pp = phytate P; Po = organic P excluding phytate; Pi = inorganic Pp is mostly degraded to Pi by bacterial phytase in the rumen (95%). However current estimation are based on in-vitro estimations In-vivo measurement are needed to take in account the impact of passage rate and physical properties of the diet (Knowlton et al., 2010) Po is represented by microbial P Assuming 85% digestibility (like microbial N) 15% undigested microbial P can represent aprox 10 g P/d losses (Bannink et al., 2012) Pi is assumed to be highly digestible The chemical form of Pi can affect digestibility Hill et al., 2008 J. Dairy Sci. 91:
23 Phosphate digestibility depends on the source Digestibility of minerals (CVB feed table 2016)
24 Solubility MSP, MCP and MDCP are the most suitable sources for ruminants because of their high solubility and digestibility
25 Biomarkers of the P status in the dairy cow BLOOD MILK BONE SALIVA RUMEN FLUID FAECES
26 Biomarkers of the P status in the dairy cow BLOOD Serum P I mmol/l adult cows mmol/l in growing cattle Serum P gives an indication of extracellular non-bone P status. Most 99% of non-bone P is intra-cellular Blood P is not representative of the real P status Sample site Jugular vein 9 14% lower than mammary or tail vein Coagulant, NaF can reduce P by 10% vs. Heparin or serum tubes Follow P and Ca in conjunction can give a better estimation on P and Ca bone resorption but still need to be investigated In case of low plasma P Extreme hypophosphatemia (haemolysis): intravenous injection of inorganic P (7 12 g P per adult cow) In other cases oral dosage of high digestible inorganic P (40 60 g/adult cow)
27 Biomarkers of the P status in the dairy cow MILK Total milk P concentration can vary between 0.7 and 1.2 g/kg milk 70 % Pi and 30 Po 50 % located in casein micelles Milk P is correlated with protein and lactose content two biomarkers However other factors can affect milk P variability individual variability, parity, stage of lactation Dietary P intake can hardly affect total milk P concentration Up to now, milk P is not a good biomarkers of the P status
28 Biomarkers of the P status in the dairy cow BONE Bones can provide good markers on P homeostasis o long term Bones respond very slowly to actual P balance by increasing or decreasing mineralization Osteoclast activity demineralization Osteoblast activity mineralization Not suitable to be used as marker of the actual P dynamics in the body Give a good indication of the long-term cumulative effects of factors affecting P balance and thereby bone P content Bone biopsies are difficult and take Plasma biomarkers of bone turnover have been identified (CTX, BSALP) and might also be used
29 Biomarkers of the P status in the dairy cow Saliva Rumen fluid Saliva P concentration depends mainly by plasma P concentration and total saliva production Rarely < 0.5 mmol/l Difficult sampling (i.e. feed contamination) Rumen fluid Dietary P concentration Saliva production Blood P concentration
30 Biomarkers of the P status in the dairy cow Urine Faeces Urine P concentration very low and not representative of P status Affected by other factors i.e. aciduria (use of phosphate to buffer urine) or hypocalcemia ( PHT, P excretion) Faeces Most relevant excretion route for P next to milk Kg faeces/d x g P/kg faeces = g P/d acuurate measurement (in experimental conditions) Can provide information on the chemical form (Po or Pi) Good indicator probably most suitable in experimental conditions
31 Take Home Messages P, Ca and Mg play a fundamental role in milk production and their proper management is essential to maximize productivity Although P and Ca absorption are decoupled, P, Ca and Mg metabolism are tightly related Mg and Ca interact with P metabolism mainly by PTH mediation Hypocalcaemia trigger the release of PTH which in turn increases P excretion by kidneys Fine and soluble Mg is needed to maximize Ca absorption and thereby optimize P metabolism Transition phase is the most sensible production phase Negative P balance, high Ca requirements, high milk production, high passage rate High efficiency of the Mg source, high digestible P Monitoring P status is not easy Blood P and Ca (in conjunction) can help to give an aproximate idea of the P status Faeces P excretion is a better measurment but total fecal collection is needed
32
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