Metabolic and Management Challenges of Periparturient Cows Denise Rich – therichartist.com Michael Overton, DVM, MPVM Associate Professor, Dairy Production Medicine University of Georgia, College of Veterinary Medicine Management Timeline for Dairy Cattle Dry-off Far dry period Close-up (3 weeks prior to calving) Transition Transition Calving Period Fresh period (3 weeks after calving) Lactation Milk Production Reproduction Metabolic Changes and Challenges Facing the Periparturient Cow � Rapid fetal growth � Hypocalcemia � Decrease in DMI � Immunosuppression � Initiation of lactation � Negative energy balance � Hormonal changes � Fat mobilization � Colostrum production � Liver challenges � Exposure of teats and � Increased risk of… uterus to pathogens � Ketosis Milk fever � Sudden demand for calcium � Diet/ rumen changes � Metritis Mastitis � Poor milk production � Pen moves � Repro challenges � Culling/ death � Etc 1
Key Points for This Presentation � Transition cows undergo extreme changes and challenges during the transition period � Energy (glucose) and calcium needs dramatically increase despite drops in feed intake despite drops in feed intake � Excessive mobilization of fat presents challenges to the liver’s capacity to make glucose � Management needs to focus on ways to improve metabolic health of transition cows Overview of the Adaptations at Parturition and Onset of Lactation (Bauman and Currie, 1980; Bauman, 2000; Ingvartsen and Andersen, 2000) Rumen: Adipose Tissue: � size � lipolysis � absorptive capacity � de novo fat synthesis � rate of nutrient absorption � uptake of preformed fatty acids � re-esterification of fatty acids Liver: � size Muscle: Mammary gland: � rate of gluconeogenesis � glucose utilization � protein synthesis � # secretory cells � protein synthesis � ketogenesis � protein degradation � nutrient use � supply of blood Ruminants are Quite Unique � ~ 90% of the carbohydrate carbon that becomes available for metabolism by the cow is in the form of VFA’s � Very little glucose available for absorption � Most is modified (fermented) by rumen microbes � Cows are very dependent on gluconeogenesis for maintaining blood glucose levels 2
Cows Rely on Hepatic Gluconeogenesis to Meet their Glucose Needs Gluconeogenesis – the pathway consisting of enzyme-catalyzed reactions that primarily take place in the mitochondria or cytoplasm of the liver that takes precursors and forms glucose � Propionate � Propionate Lactose (milk) L ct s (milk) � ~ 30 to 70% Fetus � Amino acids (Alanine) Nervous tissue Other energy needs � Up to ~ 30% � Lactate � Up to ~ 15% Liver � Glycerol � Normally, very small amounts Glucose When Energy Output is Greater than Energy Intake, Negative Energy Balance (NEB) � In response to energy demands, cows undergo lipolysis – breakdown (or mobilization) of fat stores � Result: � “Free” fatty acids (NEFA’s) circulating in blood � Glycerol Oxidation of NEFA � Fatty acid ß-oxidation: � Provides ATP for glucose synthesis � Stimulates gluconeogenesis from lactate and alanine (via acetyl-CoA activation of pyruvate carboxylase) � ß-Oxidation : pathway that sequentially removes two-carbon acetyl-CoA units from a long-chain fatty acid (acyl-CoA) � Complete combustion (oxidation) of NEFA generates Acetyl-Co A that can be used to generate energy via the Krebs Cycle � If Krebs Cycle gets overloaded, acetyl Co A is shunted off to produce ketones (acetoacetic acid, acetone, and BHBA) 3
Fetal Needs During Late Pregnancy � Fetal metabolic rate (weight-specific oxygen consumption) ~ 2X the dam � Most energy and nitrogen needs of the fetus for growth/ metabolism supplied by glucose (and lactate) and amino acids from maternal circulation acids from maternal circulation � Glucose uptake – passive � AA uptake via active placental transport (independent of maternal blood concentration) � During hypoglycemia, fetus makes up by using more AA for energy � Fetus cannot take direct advantage of mobilized maternal lipids Bell, 1995 Despite Increasing Needs, Feed Intake Drops Dramatically Prior to Calving DMI Drop is Greater in Mature Cows and in Fat Cows Normal cows: Ex: 13 kg to 9 kg -Often see drops of 25% (i 25% (i.e., DMI DMI declines to 70-75% of original level) Fat cows (BCS >3.75): -May drop by > 40% of DMI at -21 days Grummer Around Calving, Cortisol Levels Increase � Cortisol induces changes in mammary cells � Promotes maturation of the fetal lungs Promotes maturat on of the fetal lungs � Promotes production of surfactant that is necessary for normal lung function after birth 4
Short Term Increases In Cortisol Help With Gluconeogenesis � Mobilize amino acids from extrahepatic tissues � Stimulate gluconeogenesis, particularly in the liver � Results in the production of glucose from amino acids � Inhibits uptake of glucose by muscle and fat tissue � Tries to conserve glucose (glucose-sparing effect) � Stimulates the breakdown of fat � The fatty acids released by lipolysis are used for production of energy in tissues like muscle, and the released glycerol provide another substrate for gluconeogenesis Periparturient Immunosuppression Increased cortisol � � migration of leukocytes � � phagocytosis � � IGF-1 � Protein/ energy/ vitamin/ mineral � deficiencies: � neutrophil migration and killing ability � � lymphocyte function � Spike in estradiol level � Suppress cell-mediated immunity � Depresses appetite � Lower levels of vitamin A & E at calving � Partly from colostrum demands � Higher consumption due to metabolic/ � immunologic stress Goff and Horst, 1997 Periparturient Calcium Needs � Dry cow Ca needs – only ~ 10-12 g/ day � Around calving – cow must bring ~ 30 g Ca/ d into the Ca pool � A cow producing ~ 2.5 gallons colostrum loses ~ 23 g Ca A cow producing 2.5 gallons colostrum loses 23 g Ca in a single milking � ~ 9 X the total plasma level of Ca in a cow � To make up the difference, cows need to absorb more from intestine and mobilize bone � Hypocalcemia (clinical and subclinical) impact DMI and immune function) Horst et al, 1997 5
After Calving, There is a Rapid Acceleration in Nutrient Needs � Within a few days of calving, mammary requirements are increased as compared to uterine demands just before calving: � Glucose Glucose - 2.7 X gravid uterus .7 X grav d uterus � Amino acids - 2.0 X gravid uterus � Fatty acids - 4.5 X gravid uterus � Total “Energy” – ~3 X gravid uterus � Despite these needs, feed intake is low � Negative energy balance: -10 to -15 Mcal/ d (or more) � Negative protein balance: - 500 to -600 g/d (or more) Predicted Whole-Body Glucose Demand and Supply During Transition During late pregnancy, uterus is taking ~ 50% of total maternal supply Adapted from T.R. Overton, 2001 Glucose Availability is Key � Mammary uptake of glucose at 1 DIM ~ 9X that at 1 week prior to calving � Glucose is required to make lactose � Glucose is required to make lactose � Lactose is the osmotic driver for milk production 6
Liver is Crucial in These Adaptations � The liver actually increases in size and metabolic activity Day relative to calving -21 11 22 Liver weight (lbs) ~ 19 ~ 19 ~ 21 Oxygen uptake (moles/d) 35 76 80 � Glucose release from liver increases from ~ 1300 g/d at 11-d prepartum to over 2700 g/d at 11-d postpartum Bell, 1995 and Reynolds et al, 2000 Cows Adapt to the Increasing Demand for Glucose by Shifting into a Glucose-Sparing Mode 1. Increased hepatic gluconeogenesis but reduced glucose uptake by maternal peripheral tissues � Mobilizes body protein (amino acids) for glucose production � Mobilizes large amounts of body fat � Cow’s body shifts more toward energy utilization from circulating fats � Fetus benefits indirectly – receives disproportionate amount of glucose 2. Changes in insulin levels and sensitivity Normal Roles of Insulin � General (normal) role is to increase nutrient storage and decrease blood glucose concentrations Liver Muscle Fat Carbohydrate Metabolism � Glucose uptake, � Glycogen synthesis X X X � Glycogenolysis X X X � Gluconeogenesis X Fat (Lipid) Metabolism � Lipogenesis X X � Lipolysis X X Protein Metabolism � Amino acid uptake X � Protein synthesis X � Protein degradation X � Gluconeogenesis X 7
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