Function of Mammary Secretions Dr. Howard Tyler AnS 337 Lactation Biology Teleological Approach Energetically driven processes are developed to provide a benefit Synthesis of some components Active transport of some components Milk itself Colostrum Needs of both dam and offspring Importance to Newborn Shift from placentation to lactation Provide for nutritional needs Regulate developmental processes Enhance immunological status In ruminants, reticular groove development Milk as “by-pass feed” Function of Milk and Colostrum Nutrition of neonate Exogenous immune factors Influence homeorrhetic adjustments Developmental “jump start” Different Species Have Different Milk Compositions Why? Composition of milk matches the growth needs of the young of a species a rabbit doubles its birth weight in 6 days a calf doubles its birth weight in 45 days Rabbit milk has 5x the protein of cow’s milk Cow’s milk has 2x the protein of human milk Cows milk needs to have water, iron and vitamin D added to make it suitable for human infants Species Variation Table 3. Composition of Milk from Different Mammalian Species (per 100 g fresh milk). Cow Human Water Buffalo Goat Donkey Elephant Monkey, rhesus Mouse Whale Seal Protein (g) 3.2 1.1 4.1 2.9 1.9 4.0 1.6 9.0 10.9 10.2 Fat (g) Carbohydrate (g) Energy (kcal) 3.7 4.6 66 4.2 7.0 72 9.0 4.8 118 3.8 4.7 67 0.6 6.1 38 5.0 5.3 85 4.0 7.0 73 13.1 3.0 171 42.3 1.3 443 49.4 0.1 502 Milk Composition Constituent (g/100g) Cow Goat Sheep Human Water (g) 87.9 88.9 83 88.2 Energy (kcal) (kJ) 66 276 60 253 95 396 69 289 Protein (g) 3.2 3.1 5.4 1.3 Fat (g) 3.9 3.5 6 4.1 Lactose (g) 4.6 4.4 5.1 7.2 Calcium (mg) 115 100 170 34 Species Factors Affecting Milk Composition Maturity of neonate at birth Maturity of different organs Placental type and immunological status Infant doubles weight in 20 weeks Calf doubles weight in 10 weeks Piglet doubles weight in 10 days Importance of Milk Carbohydrates In newborn, lactose must be hydrolyzed prior to absorption Lactose enhances iron absorption Sweetness index affects intake Importance of Milk Fats At birth, only absorb a portion of fats Pre-gastric esterase important in calves Gastric lipase important in infants Limited by amounts of lipase and bile salts Infants have problems with cow’s milkfat Microbicidal action of some fats High cholesterol enhances neural development Major Factors Affecting Milk Composition Completeness of milking Milk removal ≈ 4 min. for a cow % removed Time (sec) Milk Fat % Fat 30 16 7 1.4 60 41 18 1.6 120 83 61 4.8 240 100 100 11.1 Fat globules tend to clump, passage through ducts is slower Fat Proteins Sugar Composition of milk Foremilk and Hind Milk .. Fats provide satiety High fat in the hind milk ensures that the neonate feels full after suckling Low fat in foremilk encourages consumption Importance of Milk Proteins Rennin (also pepsin and chymotrypsin) induce casein coagulation with calcium phosphate Enmeshes fat and whey proteins Low casein content of human milk lowers buffering capacity Less acid required for clot formation High casein milks (cows) form firmer curds High in cysteine and taurine Coagulation of Secretions Casein coagulates as pH decreases or temperature increases When pH falls below 5.1, casein destabilizes Below 4.5 – casein salts form and milk curdles Calcium phosphocaseinate Milk forms hard curds neutral casein + Ca++ (curd) (whey) Slow release nutrient delivery Cheese making properties dependent on this Colostrum forms soft coagulum Very slow release nutrient delivery Destroys cheese making properties Peptides Peptides formed from digestion of both caseins and whey proteins are bioactive Multiple functionality Anti-microbial – including control of gut microflora Anti-viral Binding of E coli and cholera enterotoxins Immunomodulation Anti-oxidative Importance of Milk Minerals Immaturity of human renal system compensated for by low sodium content of human milk Cow’s milk high in sodium Infants regulate calcium levels in first weeks through absorption rather than excretion Iron bioavailability higher in human milk High vitamin C and lactoferrin Present as iron citrate Importance of Immunological Factors Lactoferrin antimicrobial effects Lactoperoxidase and myeloperoxidase Lysozyme Bile salt-stimulated lipase Long chain unsaturated fatty acids Phagocytic cells T-cells Other Immunological Components of Human Colostrum & Milk Cytokines Complex oligosaccharides – inhibit adherence of bacteria to cells Lactoferrin – binds Fe Lysozyme – degrades bacterial cell wall Importance of Growth Factors, Hormones, and Bioactive Peptides Epidermal growth factor Nerve growth factor Nucleotides Prostaglandins Other growth factors and bioactive peptides In Conclusion Almost all components of milk have a physiological function beyond nutrition Milk components are multifunctional Mammary secretions possess a natural “cluster” of nutrients that protect health and enhance the immune system Passive Immunity (Colostrum) Neonatal Immunity Human placenta transports IgG from maternal to fetal circulation Babies born with IgG concentration approximately 89% of adult values No transport of immunoglobulins across placenta in farm animals Offspring born with essentially no circulating IgG Colostrum provides IgG after birth Ig Concentrations in Human Colostrum & Milk IgA Colostrum (g/L) 5 – 10 Milk (g/L) 0.3 – 1 IgM 0.06 0.06 IgG 0.1 0.01 Ig Immunoglobulin (and Bioactive Peptide) Absorption 24 hr period of time for attainment of passive immunity in livestock Proteolytic activity of the digestive tract is low in newborn animals Further inhibited by trypsin inhibitors in colostrum Nutrients are able to pass the stomach without degradation to the small intestine where absorption occurs Selective Transfer of IgG Occurs in rats through binding of IgG to FC receptors in the small intestine Time dependent Non-specific absorption after birth By 3 d of age, IgG absorption favored By 7 d of age, IgG absorption selection 20X greater At 21 d of age, no intact proteins absorbed into circulation Non-selective Transfer of IgG Occurs in calves and sheep Pigs and foals selectively absorb IgG compared to other macromolecules IgG, IgM, and IgA absorbed in proportion to amounts in colostrum IgA and IgM found on enterocyte surface but not inside the cell Absorption rate decreases with increasing age Mean time to closure approximately 21 to 26 h of age Absorptive Mechanism Pinocytosis Absorbed via intermicrovillous spaces Absorption permitted by lack of terminal web in microvilli Vacuole forms around absorbed material Vacuole expands as more material absorbed Vacuole fills cell Nucleus pushed down to basolateral membrane Absorptive Mechanism Filled vacuole pinches off at luminal end Nucleus and vacuole change places Vacuole merges with basolateral membrane Enhanced by large intercellular spaces in neonatal intestine Material in vacuole is “purged” into intercellular spaces After Absorption Immunoglobulins are absorbed unchanged and enter the lymphatics Lymphatics highly fenestrated immediately after birth Enter circulation via thoracic duct In circulation, IgG is distributed equally between extraand intravascular space Equilibrium reached in 51 h IgG can be secreted back into the intestinal lumen through the duodenal crypt cells Efficiency of Ig absorption 40 35 30 25 20 15 10 5 0 0 4 8 12 16 20 24 Time (hours) relative to birth Closure Even after closure occurs, cells continue to take up colostral material into vacuoles Completed vacuoles do not exchange places with nucleus or other cellular organelles Cell migrates to tips of villi and are sloughed off and excreted Failure of Passive Transfer (FPT) Low IgG levels greatly increase risk for death and disease in ALL species 40% of calves classified as FPT (<10 g IgG/L) Colostrum-deprived calves 50-74 times more likely to die before 3 weeks of age FPT calves are twice as likely to get sick as non-FPT calves NAHMS estimates suggest 22% of all calf deaths could be prevented by better colostrum management