Lactation, Milk, and Nutrition

Week 1 January 6

Lecture 1 1-10: outcomes

  • 1. Describe why there is a need for optimal infant and young child feeding all around the world. 

  • Describe the particular problems that developing countries may face in regards to optimal infant and young child feeding. 

  • Identify the top FOUR causes of death of children younger than five years of age.

  • Define the WHO and UNICEF recommended infant and young child feeding practices. 

  • Define exclusive breastfeeding. 

  • Define complementary feeding.

  • Describe the current global breastfeeding status.

  • List the conditions which children and mothers may have an increased risk of if breastfeeding does not occur.

  • Describe the benefits of breastfeeding for the infant and the mother. 

  • Evaluate whether or not a woman may be at an increased risk of becoming pregnant by using the Lactational Amenorrhea Method of birth control. 

  • Describe the socioecological model of breastfeeding support. 

  • List the 8 MDG's and describe how breastfeeding helps to achieve each one. 

  • Describe the general breastfeeding trends (you will not be asked specific statistics). 

  • Identify campaigns that are intended to help support breastfeeding. 

  • Describe the economic benefits of breastfeeding. 

  • Describe the mechanisms by which breastfeeding can impact: obesity, cholesterol, type two diabetes, blood pressure, and IQ scores later in life. 

Lecture 2 1-12: Why Breastfeed?

  • optimal infant and young child feeding practices

    • most effective interventions to improve child health

  • in 2019 an estimated 5.2 million children dies before their fifth birthday (60% decrease from 1990)

    • ¾ of these deaths (3.9 million) occurred in the first year of life

    the goal for the sustainability for infant mortality is 25 per 1000
    • developed countries have lower infant mortality

    • the US averages around 3 per 1000

    • NC is about 6 per 1000

  • What do you think are leading cases of infant mortality

    • globally the top causes of infant death in 2010 (NIH)

      • neonatal encephalopathy, or problems with brain function after birth, neonatal encephalopathy usually results from birth trauma or a lack of O2 to baby during birth

      • infections, especially blood infections

      • complications of preterm birth

      • lower respiratory infections ( ie flu or pneumonia)

      • diarrheal disease

    • globally (WHO)

      • infectious disease including pneumonia, diarrhea and malaria along with preterm birth complications, birth asphyxia and trauma and congenital anomalies remain

    • the most common cause of death in the US in 2011 were the following (NIH)

      • birth defects

      • preterm birth and low birth weight

      • sudden infant death syndrome (SIDS)

      • pregnancy complications

      • accidents

  • the mother’s perspective

    • exclusive breastfeeding can

      • delay the return of fertility

      • accelerate recovery of pre-pregnancy

    • mothers who breastfeed exclusively and frequently have less that 2% risk of becoming pregnant in the first 6 months postpartum, provided that they still have amenorrhea

  • need for optimal infant and younf child feeding

    • under-nutrition is associated with at least 45% of child deaths

    • about 26% of children <5 years of age in developing countries are stunted and 7.5% wasted

    • suboptimal breastfeeding in the first year of life, results in

      • 1.4 million deaths and 10% of disease burden in children less than 5 years old

  • recommended infant and young child feeding practices

    • WHO and UNICEF’s

      • exculsive breastfeeding for 6 months

      • nutritionally adequate and safe complementary feedong start from the age of 6 months with continoued breastfeeding up to 2 years of age or beyond

      • the child will have more antibodies and calores

  • feeding definitions

    • exclusive breastfeeding

      • an infant receives only breast milk from his or her mother or wet nurse, or expressed breast milk, and no other liquids or solids, not even water, with the exception of oral rehydration solution, drops or syrups consisting of vitamins, minerals supplements or medicines

    • complementary feeding

      • the process starting when human milk is no longer sufficient to meet the nutritional requirements of infants

        • other food and liquids are needed, along with human milk

        • the target range for complementary feeding is generally taken to be 6-23 months of age

        • breastfeeding may continue beyond 2 years

      until 6 months 43% of the population is exclusively breastfed
  • what breastfeed for 2 years or beyond

    • for the child, not breastfeeding association woth increased risk of

      • diarrehea

      • pneumonia

      • ear infections

      • meningitis

      • urinary tract infections

      • asthma

      • type 1 diabetes

      • celiac disease

      • ulcerative colitis

      • childhood leukemia

      • obesity in childhood and adolescence

      • increased risked of heart disease later in life

      • about 4 numbers lower IQ score

    • for the mother, not breastfeeding her infant is associated with increased risk of

      • postpartum hemorrhage

      • breast cancer

      • ovarian cancer

    • developing countries

      • infants not breastfed are 6-10x more likely to die in the first months of life

  • complementary feeding

    • stating around 6 months of age the infants begin to require more calories and nutrients than what is provided in milk

    • if complementary feeding is inadequate

      • growth may falter

      • micronutrient deficiencies may increase

        • especially iron

      • infectious illness may increase

    • even with complementary feeding, breastfeeding is a critical souce of nutrients for baby/toddler

    • breastfeeding provides

      • up to ½ of infants energy needs up to 1 year of age

      • up to 1/3 during the second year

      • high quality nutrients that in complementary foods

      • immune factors

  • breastfeeding helps to achieve all millennium development goals

    • millennium developed goa

    • developed by UNDP (united nations gloabl development network)

    • in 2000, 189 nations made a promise to free people fore extreme poverty adn multiple deprivations

  • eradicate extreme poverty and hunger

    • breastfeeding reduces early childhood feeding cost

    • exclusive breastfeeding and continued breastfeeding for 2 years is associated ith reduction in underwight and is an excellent source of high quailty calories for energy

  • achieve uiveral primary education

    • breastfeeding and responsive complementary feeding are prerequisites for readiness to learn

    • breastfeeding and quality complementary foods significantly contribute to cognitive development

      • could be bc of the fats in the milk that the brain needs to grow and develop

  • promote gender equality and empower women

    • breastfeeding is a good equalizes giving every child a fair start on life

    • most differences in growth between sexes begin as complementary foods are added into the diet, and gender preferences begins to act on feeding decisions

    • breastfeeding is uniquely a right of women and should be supported by society

      • more societal constructs to allow women to breastfeed more

  • reduce child mortality

    • infant mortality coud be reduced by about 13% with improved breastfeeding practices alone, and about 6% with improved complementary feeding

    • in addition, about 50-60% of mortality in children < 5 years is secondary to malnutrition

      • poor breastfeeding practices

      • inadequate complementary foods and feeding

  • improved maternal health

    • the global WHO demands increased attention to support the mothers nutritional and social needs for increased reproductive health and nutritional and pregnancy outcomes

    • breastfeeding is associated with:

      • decrease maternal postpartum blood loss, decreased breast cancer, ovarian cancer, endometrial cancer, and the probability of decreased bone loss post-menopause

    • breast feeding promoted healthy birth spacing

      • reduced maternal risks of pregnancy too close together

  • combat HIV/AIDs, malaria, and other diseases

    • compared with artificial feeding, breastfeeding during the first 6 months by HIV-positive mothers increase HIV-free survival by 32 per 1000 live births

    • after 6 months, as the age-specific mortality rate and risk of death caused by replacement feeding both decline, replacement feeding appears to be safer

      • also depends on access to antiviral mediations

    • low uptake of the virus during exclusive and high uptake during complementary feeding

  • ensure environmental sustainability

    • breastfeeding is associated with

      • decreased milk industry waste pharmaceutical waste, plastics and aluminum tin waste, and excess use of firewood/fossil fuels

  • develop a global partnership for development

    • support breastfeeding including

      • the global strategy for infant and young child feeding

      • the surgeon general’s call to action to support breastfeeding

      • socio-ecological model

    • fosters multisectoral collaboration

    • builds up the existing partnerships for support of developments

    • optimal infant feeding has major implications future economic productivity

  • economic benefits of breastfeeding

    • reduced health care related expenses

    • reduced time off to care for sick infant

    • benefit for employers

      • lower maternal absenteeism

      • increased employee loyalty

      • improved productivity

      • lower insurance premiums

      • enhanced public image

    • health care payers or insurers would benefit savings in:

      • physician fees

      • emergency room fees

      • prescriptions

      • laboratory procedures

    • long term health care savings

      • less chronic diseases

  • estimates of health care saving

    • USDA estimates that >$3.6 billion could be saved of rates were increased to levels recommended by US surgeon general

      • estimate could be higher. only representants savings for ear infections, gastroenteritis, and NEC

    • if all women participating in WIC breastfed for 1 month, $30 million would be saved

      • an additional %48 million if 75% of WIC mothers breastfed for 3 months

    • breastfeeding reduces high cholesterol, hypertension and blood pressure, chances of being overweight, type 2 diabetes, and decreased IQ scores

  • effect pf breastfeeding on obesity later in life: mechanisms

    • lower protein and energy intake among breastfed

      • higher protein intake in infancy may increase obesity later

    • breastfed and formulates infants have different hormonal responses to feeding

      • formula feeding leads to a greater insulin response

        • increase fat deposition and increase adipocytes (fat cells)

    • breastfed infants adapt more readily to new foods such as vegetables

      • reduces the caloric density of their subsequent diets

  • effect of breastfeeding on blood pressure later in life: mechanisms

    • sodium content? - no consensus

    • fatty acids content of human milk - PUFAS

      • important structural component of the vascular endothelium

      • studies are mixed regarding health effects of PUFA added to infant formula - may not act the same

    • breastfeeding has protective effect on obesity

    • insulin-like growth factor (IGF-1) is inversely related to blood pressure in adulthood

      • IGF-1 later in life is positively associated with breastfeeding

      • IGF-1 programming may lead to lower blood pressure

  • effects of breastfeeding on cholesterol later in life: mechanisms

    • cholesterol content is markedly higher in human milk than in most commercially available formulas

      • high cholesterol intake in infancy may have a long-term programming effect on synthesis if cholesterol by down-regulation of hepatic hydroxymethylglutaryl coenzyme A (HMG- CoA)

        • HMG- CoA is the rate-limiting enzyme in synthesis of cholesterol from acetate

        • animal studies show that early exposure to increased levels of cholesterol is associated with decreased blood cholesterol levels at a later age

  • effect of breastfeeding on type 2 diabetes later in life: mechanisms

    • breastfeeding increases LCPUFAs in skeletal muscle membrane, which decrease fasting glucose

      • early changes in skeletal muscle membrane may decrease insulin resistance, beta-cell failure, and type 2 diabetes

      • formula fed infants have higher concentrations of inulin, which may increase the risk of beta-cell fail and type 2 diabetes

      • adjusting of obesity reduces the strength of the breastfeeding association

  • effect of breastfeeding on IQ scores later in life: mechanisms

    • LC-PUFAs are preferentially incorporated into neural cell membranes; structural lipids constitute about 60% of the human brain

      • docosahexaenoic (DHA) and arachidonic (AA) acids are important for retinal and cortical brain development

    • breastfeeding enhances the bonding between mother and child, which may contribute to the child’s intellectual development

Week 2 January 14

Learning objectives

Lecture 3 1-17: why drink milk

  • review: which factors apply to adults and cross species milk consumption

    • the bonding between the mothers and child through breastfeeding also promotes learned skills

  • review life cycle

    • which factors apply to adults and cross species milk consumption and which species

      • appropriate nutrition (includes proteins, fats, and calories) and preventing appropriate disease (ie bacteria in yogurt and bioactive proteins)

      • learned skills taking what you know from the dairy industry and applying it to other fields of agriculture and growing food

      • cows, goat, camel

        • camel milk can be used for its antidiabetic factors

      • moose in Siberia

      • horse and donkey milk is proscribed for Anti disease functions

        • say that dairy is important to the diet for high quality protein and minerals that might be provided in low income countries

          • most people in those contries will consume food with high levels of starch

        • milk can be expensive so milk powder can be used as a substitute

    • tells people to drink skim or 1% milk because the nutrients are provided and people tend to think milk is a very fatty food

      • talks about less fat same amount nutrients (tries to stick to the recommended 2000 cal diet)

      • how to get the 3 cups

        • top fruit salads and baked potatoes with low-fat yogurt

        • if lactose intolerant try lactose-free milk or fortified soymilk

  • health benefit of drinking milk

    • improved bone health, and may reduce the risk of osteoporosis

    • important to bone health during childhood and adolescence, when bone mass is being built

    • associated with a reduced risk of cardiovascular disease and type 2 diabetes and lower blood pressure in adults

  • nutrients from milk

    • calcium is used for building bones and teeth and in maintaining bone mass

    • diets rich in potassium may help to maitain healthy blood pressure

    • vitamin D functions in the body to maintain proper levels of calcium and phosorous, thereby helping to build and maintain bones

      • vitamin D is added to millk a lot of time bc cows dont produce that much and people tend to be defficent

  • RDA (recommended daily allowance) in 3 cups of whole milk

    • nutrient density is the measure of the amount of beneficial nutrients in a food product in proportion to its energy content, weight or amount of detriment nutrients. it is a way of evaluating the nutrient quality of food by comparing the amount of nutrients consumed in a bite a meal or day

      • milk is nutrient dense in protein, calcium, phosphorus, zinc, riboflavin vB12), vD

      • vD is fat soluble so vD added to whole milk will likely enter your body instead of 1% it will prolly be sticking to the sides of the container

  • what’s special about milk’s nutrition? disease prevention

    • malnutrition

    • bioactive components relating to various disease:

      • rickets, osteomalacia, osteoporosis

      • metabolic syndrome, obesity, cardiovascular disease, hypertension and type 2 diabetes

      • oxidative and inflammatory stress

      • regulate satiety and digestive

        • satiety: the feeling of fulness and satisfaction after a meal

      • processes

      • cancer (Ca, [H,X]AMLET human milk protein) (particularly colon cancer)

      • dental caried

  • evolutionary considerations

    • pre-human 3.2 million years ago were probably omnivores

      • time of finding Lucy the hominid

        • walking upright

          • carying an infant and breastfeeding while moving

    • cattle depicted in drawings about 30,000 years ago

      • important part of the culture

      • do not know if the meat or milk was consumed

    • domestication of livestock happened about 10,000 years ago

      • holding animals for their whole life and then breeding them

    • milk adopted as human food about 6,000 years ago

      • we know this from artifacts

        • had traces of milk proteins

  • History of dairying

    • animal domestication - milk, meat, blood, hides, wool, muscle power

    • dairy domestication occurs around the world

      • species and breed differences

    • persistent lactasia (lactose digesting capacity. LDC) - mutation in human regulatory sequence (intron) that permits adult lactose utilization

      • single nucleotide mutation

      • when the animal is weaned, the genes turn off from being able to digest milk

        • mutation began in the yt people

    • dairy domestication occurs around the world - species and breed differences

    • cattle transported with population migration - animals were wealth, wealth generating

      • most early Americans and European families held a few cows for family use

        • had to transport animals on the boats for 1-2 months

      • milk is perishable commodity - use right away

        • northern climates favored

        • seasonal breeding

          • good bc animals like goats don’t require as much fed but you would have to find another milk source

        • most milk consumed in the colder months and less in the summer months

    • urbanization hastens innovation

      • larger farms, transport, distribution

      • mechanization: feeding, milking, packaging

    • sanitation: benefit consumers and animals

      • developed in the early part of the 20th century to increase shelf life and prevent spoiling

      water buffalo made for dairy; some of their genetics are used in cows for heat tolerance
      • Pakistan is 2nd in total milk production if you add up all the animal’s milk

    • highest production in April and May with the least being in October and November

      • cows are being rebreed

      • in January and February milk increase as the cows calve

    • cows are producing more milk due to better genetics

    • highest cost of milk is processing

  • US - milk marketing

  • USDA report: US farm numbers continue to decline

    • California is the biggest producer - 2% increase; 41.3 billion lb.

    • Wisconsin - 18% increase in milk production; 30.7 billion lb.

    • Texas - 68% increase in milk production; 14.8 billion lb.

    • New York -15.38% increase in milk production; 15.3 billion lb.

    • Idaho - 27% increase in milk production; 16.2 billion lb.

  • developing countries - appropriate, species, breeds, management

    • collection from small holder dairies

    • milk bulking centers

    • test quality

    • record payment

    • breeds

      • Malawi zebu (Malawi)

        • people are trying to improve genetics my mixing genes with other breeds like the Holstein

      • Finnish Friesian (Finland)

      • Holstein Friesian (Germany and the Netherlands)

      • milk yield consideration

      • heat tolerance in tropical developing countries

      • adequate diets necessary

        • energy for maintenance (forge)

        • milk for calf (forage)

        • extra milk for collection (forage + concentrations)

      • milk uses

        • family

        • vendor sales (immediate money)

        • coop bulking groups

          • pasteurization and processing

          • monthly check

  • dairy farm energy

    • energy flux

      • farm system

        • how the operation works

        • Maintenace

        • storage of milk

      • pictures

      • calculation basis

        • how the energy goes in and out of the dairy farm

        • electricity, feed, and human components (labor, capital, vet services) are the inputs

      • calculation basis: NCSU dairy unit

        • milk production -80 lb./day Holstein + 65 lb./day jersey (average = 75 lb./day)

        • 75 lb./day or 34 kg/day x 625 cal/kg = 21,250 cal/cow/day

        • 160 milking cows x 21 kcal/day = 3360 kcal/day

  • conclusion

    • system flows mainly from feed to manure and energy loss represents 61% as heat and 23% as manure from total inputs

  • why drink milk

    • milk is life sustaining food

    • milk is rich in essential nutrients

    • retail milk is sanitary and ha uniform quality

    • milk taste good to most people

    • physical and chemical properties allow transportation and processing in massive quantities with minimal labor

    • much of US and other temperate countries are good for dairy relative to other crops

Lecture 4 1-19: human milk composition and correlation to reducing infant mortality

  • human milk and formula

    • the differences in the microscope pictures are bc of

      • cellular protein and nucleic acids straining unevenly and darker blue in human milk

        • white is fat bc fat does not stain

        • the proteins and nucleic acids are stained

      • bacteria and cell debris are removed from bovine milk before it is processed into infant formula

        • processing includes putting the milk through a centrifuge to remove the somatic cells and bacteria

    HMO = human milk olisaccarides
    • cow’s milk has more minerals

    • same osmolarity

    • some people made their formula from cows’ milk

      • dilute it and then and some sugar or sucrose and some fat

      • carbs pull water

      • 1940s-1970s

    • blue whale milk is thick

      • high casein (protein)

      • not very osmotic

    • horse milk is similar to human milk

    • less calories in milk means slower growth rate

    • humans and horse milk provide all the water an infant needs

    • protein drops

    • carbs increase

    • a big drop in sodium from colostrum → mature milk

      • helps with water intake

      • water will follow the sodium

      • the tight junctions in the infant are still leaky so the sodium leaks from the blood into the cell

    • more calcium more casein

  • lipids

    • largest source of energy in human milk

      • contributes 40-55% of the total energy

      • for adults it is less than 30% of the recommend total energy

        • in the form of triglycerides

        • has an ester bond

        • cow’s milk has a lot of short - medium carbon side chains (C6-C12)

        • plants are normally C16-C18

        • a lot of research is going to see if changing the lipid composition plant vs cow will have an effect on the human body

          • brain effects also

          • when C6-C12 is absorbed in the intestines they are small enough to stay within the blood stream

          • C16-C18 has to be repackaged into triglycerides into chylomicrons to be transported within the bloodstream

    • contains over 200 fatty acids

    • oleic acid dominates (C18:1 omega 9)

    • long-chain PUFAs

    • short-chain fatty acids

    • sphingomyelins

    • functions

      • allow maximum absorption of fatty soluble nutrients

      • provide essential fatty acids and polyunsaturated fatty acids

        • omega 3 and omega 6 are essential

      • provide cholesterol

        • plants do not make cholesterol

      • neonatal cell membrane production needed for growth, brain and retinal development, and bile salt synthesis

        • linked with cell growth

      • nervous system myelinization

  • contains over 200 fatty acids

    • from 6 to 24

    • different chemical structures if you go from unsaturated (has the double bond) to saturated

      • monounsaturated fats in the omega 3 position (meaning the double bond is 3 carbons away from the methyl end)

    • PUFA = polyunsaturated fatty acid

    • very small amounts of odd chain FA

      • 15 and 17

    • linoleic acid is an essential omega 6 FA (18:2n-6)

    • alpha linolenic acid is an essential omega 3 FA (18:3n-3)

    • what biological or environmental factors might be responsible for an increase in essential fatty acid composition of human milk samples over the years 1945 to 2005

      • changes in diets to increase plant oil use in foods and in cooking and less of saturated fat from animals

        • lard is from pigs

        • Talo is from cows

  • human milk lipids are dynamic

    • fat content is higher in the evening than in the morning

    • the type of fat consumed

      • a diet rich in PUFAs will cause an increased percentage of PUFAs in the milk without affecting the total fat content

      • when fish oil is given during pregnancy, it significantly increases omega-3 FA and IgA as well as other immune factors

    • the ratio of PU to saturated fats in human milk promotes calcium absorption

      • calcium absorption is depressed by 4.5 P/S ratio found in bovine milk

  • human milk lipids have antiviral activity

    • potent cytolytic effects on intestinal parasites and gram-positive bacteria and yeast

    • lipids in fresh human milk do not inactivate viruses until storage at 4 C or 23 C due to the release of FFA from milk triglycerides

      • level of lipoprotein lipase in milk was correlated with he antiviral activity of the milk TG→FFA

      • antiviral effect is caused by disintegration of viral envelopes by FA

  • carbohydrates

    • primary source of calories in human milk

    • lactose is the predominant carb

      • easily digested

      • facilitates calcium absorption

        • binds with calcium in the disaccharide form

      • essential for CNS development

      • reduces osmolarity relative to monosaccharides

      • more slowly digested than sucrose or maltose

  • proteins

    • over 400 proteins in human milk

    • casein (10-50%)

      • about 5 different monomers to form casein in cows

      • human milk has lower amounts of casein than bovine milk

    • whey (90-50%)

      • alpha-lactalbumin (helps make lactose)

      • beta-lactalbumin (not present in humans only cows)

      • lysozyme

      • serum albumin

      • 50% in colostrum and 90% in mature milk

    • enzymes

    • hormones

    • IgA (32x higher in human milk than in bovine milk)

    • IgG

    • IgM

    • cytokines

    • growth factors

    • anti-inflammatory factors

  • proteins and AA in human milk have several functions

    • nutrition (provides 4 cals per gram)

      • after digestion and absorption

    • antimicrobial and immunomodulatory activities

      • in gut and post absorption of nutrients

        • example for protein: vB12 binding protein

        • example for AA: zinc and histidine

  • vitamins and minerals

    • vitamins

      • most vitamins avaliable in sufficient quantities in human milk

      • cows milk is less diluted and contains the same if not more minerals

      • vD - supplementation recommended by AAP

      • vK - present in small amounts in human milk

        • protection from hemorrhagic disease

    • minerals

      • iron - levels in human milk are sufficient to meet the iron requirements of the exclusively breastfed full-term until 6 months of age

        • most formulas are iron fortified bc bacteria can’t grow without it

          • harder for absorption

      • fluoride - in communities with fluoridated drinking water, breastfed babies receive fluoride through their mother’s milk

  • whats in infant formula

    • fat free milk, add lactose, add whey, add oleic acids (has omega 6) cohni oil (for DHA) and alpina oil (for arachidonic acid), HMOs (oligosaccharides such as fructooligoaccarides and 2’-fucosyllactose), beta creatine (vA precursor) lutein and lycopene (bioactive nutrients and accumulate in the retina), potassium citrate (for some fat), calcium carbonate ( for calcium), ascorbic acid (vC), soy lecithin (emulsifier for fat), potassium chloride to balance the P:K ratio, magnesium chloride (Mg an essential nutrient), ferrous sulfate (for iron), choline (for phospholipid synthesis and neurotransmitter), ascorbyl palmitate (vC), taurine (AA high in human milk for vision), tocopherols (vE), potassium hydroxide (to balance pH), nucleotides (found in human milk but not bovine milk)

  • HAMLET: human alpha-lactalbumin made lethal to tumor cells

    • complex of alpha-lactalbumin and oleic and linoleic acid

    • can increase the activity of antibiotics against methicillin-resistant staphylococcus aureus (MRSA)

    • broad anti-tumor activity (does not affect healthy cells)

  • cells

    • babies ingest thousands-millions of immune cells from their mothers daily

    • immune cells increase significantly in milk when the mother baby has an infection

  • glycoproteins

    • mucins: protect against infection, regulate cellular signaling, and transcription (glycoprotein that complexes bacteria)

    • bile salt stimulated lipase (BSSL): aids in lipid digestion and inhibits virus invasion (breaks down the triglycerides and fatty acids)

    • lactadherin: binds to rotavirus and inhibits its replication; stimulates growth of intestinal epithelial cells

    • lactoferrin

  • lactoferrin

    • iron chelation to assist in iron absorption in the infant and inhibit bacterial iron absorption

    • modulator of inflammatory and immune responses

    • protects against tumor growth

    • aids in one development

    • the peptides also seem to have an antibacterial agent to them

  • immune factors

  • secretory IgA

    • in the gut and found in human milk

    • mother is exposed to pathogen → mother makes antibody to pathogen → mother breastfeeds baby → baby ingest antibody → baby is protected from specific pathogen

  • lysozyme

    • breaks down the outer cell wall bacteria

    • human milk contains 3,000x more lysozymes than bovine milk

    • resistant to break down by acid in the stomach as well as trypsin

      • adequate amounts reach the intestinal tract

      • breaks down cell wall of gram positive bacteria

  • select defense molecules

    • mucins

      • inactivates viruses and bacteria

    • fibronectin

      • makes phagocytes more aggressive against microbes

      • helps repair tissues damaged by immune response

    • bifidus factor

      • fosters growth of lactobacillus bifidus in gut

    • gamma-interferon

      • enhances antimicrobial activity of immune cells

      • one of the first things to be produced during an immune response

    • B12 binding protein

      • reduced amount of B12 available to harmful bacteria

  • leukocytes (white blood cells)

    • Phagocytes

      • b lymphocytes

        • produce antibodies against specific microbes, especially E. coli

      • T lymphocytes

        • kill infected cells directly and mobilize the immune system

    • lymphocytes

      • neutrophils

        • attack and digest bacteria

        • most abundant in colostrum

      • macrophages

        • kill microbes in baby’s gut

        • produce lysozyme and mobilize the immune system

  • adiponectin

    • inversely related

    • more adiponectin less body fat

  • effects of breastfeeding on blood pressure later in life: mechanisms

    • FA content of human milk

      • PUFAs are protective of high blood pressure

    • breastfeeding has a protective effect on obesity

      • may then lead to protective effect on blood pressure

  • adapts to baby’s needs

    • hindmilk has more fat

  • stages of human milk

  • pre-term milk

    • composition similar to that of colostrum

    • higher levels of IgA, lactoferrin, and lysozyme

    • LC-PUFAs are higher and remain higher for the first 6 months in women who deliver preterm

    • 24 calories per ounce

  • human milk composition changes with individual variation in second year lactation

  • time-associated changes in human milk

    • time since the last feeding

      • the more time that has passed since the last feeding, the lower the concentration of fat in the milk

    • diurnal variation

      • fat content peaks midmorning

      • fat content is lowest in the middle of the night

  • hormones

    • prolactin

      • the milk making hormone and the mothering hormone

      • levels are higher at night

    • CCK

      • signal satiation after feeding

    • melatonin

      • levels are higher at night

      • it has a hypnotic effect as well as a relaxing effect on then smooth muscle of the gastrointestinal tract

  • oxytocin

    • associated with

      • lower blood pressure

      • vasodilation

      • metabolic

      • effects

      • anti-inflammatory properties

Week 3 January 21

learning objectives

Lecture 5 1-24: nutritional components in milk

Article notes from lecture

  • residential green environments are associated with human milk oligosaccharide diversity and composition

    • HMO = human milk oligosaccharides

    • breast milk composition is impacted by the living environment

    • green environments (with varying levels of environment microbiota) may influence the abundance and composition of microbiota that colonize the maternal skin and respiratory tract leading to changes in the maternal immunity and milk microbiota

    • green environment may also influence the concentrations of other components in milk such as pollutants which interact with HMOs within milk → changes in HMO diversity and concentration

      • ie bacteria from trees is different from bacteria on concrete

    • modifications in HMO composition may further impact infant gut microbiota composition and immunity impacting on risks of several childhood disease

    • 1)greenness (normalized difference vegetation index NDVI)

    • 2) vegetation cover diversity (VCDI)

    • 3) naturalness index (NI)

      • the main HMO secreted is 2-fucosyllactose

        • nondigestible by the gut

        • becomes a prebiotic to feed the gut

        • people make a lot of 2-FL are known as secretors

        • people who do not produce a lot of 2-FL are Non secretors

          • the environment affects them more

    • based on this reading of an infant formula ingredient label in an earlier lecture, what components were identified as additives to account for the difference in the amount of oligosaccharides secreted into milk of cows relative to humans?

      • 2’-fucosyllactose and fructooligosaccharides

  • oligosaccharides

    • serve as a prebiotic for development of friendly gut bacteria

    • binds pathogens and prevents them from binding to the gut

    • third most abundant ingredient in human milk

    • made up of fucose, galactose, hexose, glucose, sucrose, galactose

    • lots of binding sites

  • whats in human milk

    • HMO are food for freindly bacteria like bifidobacterium infantis. shorter chain HMOs in particular are almost entirely consumed by this microbe

    • prebiotic

      • non-digestible food ingredients that stimulate the growth and activity of designated species of beneficial bacteria

      • HMOs

    • probiotic

      • living organism which when administered in adequate amounts confers a health benefit on the host

      • breast milk bacteria

    • human milk has significantly more oligosaccharides than other species milk

  • breast milk microbiome

    • hundreds of bacterial species

      • varies greatly between individuals

    • composition changes over the course of lactation and is affected by obesity and mode of infant delivery

    • probiotic action

      • human milk is a source of beneficial bacteria that can colonize the infant gut

  • nutritional role of the normal infant gut microbiome

    • HMOs and milk from primates have an effect on the nutrition of the infant, the infant is having an effect on the growth of the microorganism, and the microorganisms have an effect of what nutrients are available in the infant’s gut

  • where does vB12 come from?

    • vB12 synthesis

    • comes from mostly animal products bc mammals can’t produce it → comes from microorganisms

    • beef has a lot of B12 because they are ruminants

      • important for DNA replication, red blood cell formation, and development and normal function CNS

      • number of genes involved in B12 synthesis within microbiome increases with age

  • where does folic acid come from?

    • folate synthesis (vB9)

      • involved in DNA replication and repair and erythropoiesis

      • microbiome may synthesize a pool of folate that represents around 63% of adequate intake level for infants less than 5 months of age

      • found in foliage

      • in plants it is attached with complex with glutamic acid

        • bacteria probably produce the form with polyglutamate

      • animals will eat their own feces to ingest and absorb more B12 and folic acid

    • which class of organisms that is contained in human foods is able to synthesize the vitamin folate

      • bacteria

      • plants

      • fungi

    • what is the class of organisms that is principally responsible for synthesis of the vB12 that is a needed component of the human diet

      • bacteria

  • health associations with microbiome dysbiosis

    • childhood obesity

    • necrotizing enterocolitis (NEC)

      • the degradation of the gastrointestinal tract due to bacteria

      • common in premature babies

      • one of the leading causes of death in premature babies

    • intestinal bowel disorder (IBD)

    • Crohn’s disease

lecture

  • topics

    • composition: proteins, lactose, lipids, minerals, vitamins, enzymes

    • factors affecting composition: species breed, feed, stage of lactation

    • physical and chemical properties: density freezing point, color, pH, acidity, flavor

    • bacteria

    • somatic cells and microorganisms: lactobacilli, history, significance in cultured products

  • milk fraction terms

    • plasma: milk - fat (skim milk)

    • serum: plasma - casein micelles (whey) are taken out

      • plasma minus the coagulatable proteins

    • solids-non-fat (SNF): protein, lactose, minerals, acids, enzymes, vitamins

      • it is the total solids content minus the fat content

    • total milk solids: fat + SNF

      • 86% in bovine

  • composition tables

    • human is about 4.5% fat

      • 87.1% water

      • casein is 0.4%

      • whey is 0.5%

      • lactose is 7.1%

      • ash is 0.2%

      • energy (kcal/100g) is 72

      • high lactose low ash

    • cow (bos taurus)

      • 87.3% water

      • 3.9% fat

      • 2.6% casein

      • .6% whey

      • 4.6% lactose

      • 0.7% ash

      • energy (kcal/100g) is 66

      • low lactose high ash

    • ash is made of the minerals, vitamins and electrolytes

  • composition of bovine milk

    • casein is 80% of the protein in the milk and whey is 20% in bovine

    • in humans is 80% whey and 20% casein

    • non-protein nitrogen is from urea, nucleotides, small nitrogen molecule containing molecules

    • N in protein makes up 17-18%

      • the conversion factor is 6.38 in milk

      • whereas in most food its 6.25

      • this is because of the different composition of casein compared to most proteins

  • lactose

    • most abundant of milk solids

    • made up of galactose and glucose

    • beta 1-4 glycosidic bond

    • disaccharide and cannot cross the cell membrane of the alveoli

    • hydrolases break the glycosidic bond in the gut

  • lactose hydrolysis increases sweetness in milk

    • the more hydrolase the more it breaks down lactose into galactose and glucose

  • milk proteins

    • casein and whey

      wheywhey
    • whey

      • alpha helix

      • beta barrel is used as a binding site

        • any molecules like lipids, vitamins will bind here because the beta barrel is hydrophobic

      • a-lactalbumin binds calcium, zinc, and manganese

        • important to form lactose

    • casein

      • the inside of the casein submicelle is a hydrophobic core

      • has alpha and beta casein

      • the outside layer of the is called kappa casein or k-casein

        • glycoprotein

        • helps to form a micelle

      • the micelle keeps the protein suspended in the milk at regular pH

        • when the pH is changed the micelles with come together

          • happens in the stomach

          • that’s how you get milk curds

  • lysozyme

    • breaks down the other cell wall bacteria

    • human milk contains 3,000x more lysozyme than bovine milk

    • resistant to break down by acid in the stomach as well as trypsin

      • adequate amounts reach the intestinal tract

      • a lot in human not so much in bovine milk

      • beta-lactoglobulin is really resistant to digestion and alpha-lactalbumin is easier to digest

  • predominant proteins in human and bovine milk

    • bovine has more casein that human

    • barely any lactoferrin in bovine

    • cystine makes disulfide binds to form alpha helixes

    • human milk tends to have beta-casein

  • milk proteins-reactions

    • destabilization of the casein micelles

    • change in pH

      • the isoelectric point (pI) of milk is around 4.5

      • so below 4.5 the casein will be protonated and lose its negative charge

      • as a result, it destabilizes the kappa casein and makes the micelles come together making curds

    • proteolysis (rennin)

    • glycomacropeptide

      • enzyme used to destabilize kappa casein and allows the milk to curd

    • originally got rennin from calf stomachs but now it is made synthetically

  • lipids

    • fat soluble vitamins

    • saturated FA

    • butyric acid, SCFA, VFAs

    • trans FA, CLA, rumenic acid

      • is a cis/trans isomerization in the rumin when fed linoleic acid (PUFA from soy oils)

      • reduces the double and then the double bond can reform

      • when the rumen forms TFA they are healthy

      • not found in human milk

      • can have anti caner properties

    • sterols

    • essential fatty acids

  • milk fat

    • milk fat globule

    • protein membrane

    • rupture of FGM (fat globule molecule)

    • density (fat is less dense than water)

      • in milk at the store the milk goes into a centrifuge and is homogenized

      • the bigger fat globs are broken up into smaller ones and coated by casein

      • in raw milk the bigger globs are lighter that water will float to the top and make a cream fraction

    • composition

      • most is made from triglycerides

        • back bone is glycerol

        • combined with a free fatty acid

        • combined with an ester bond

        • synthesized from within the cell

        • the mammary gland can synthesize its own triglyceride like in adipose tissue and in the gut

        • the 2 positions in the carbon tends to polyunsaturated fat and long chain fatty

        • the short chain FA tend to form on the outside

    • saturated and unsaturated fatty acids

      • one double is in the cis so that that the Carbon and Hydrogen stay in the same side

      • stearic acid the saturated form of an 18 carbon FA

    • principal fatty acids in milk fat

      • the fatty acids are named based on their length

      • short chains are made from acetic acid

      • mammary glands tend to synthesize medium and short chain fatty acids

      • neither human nor bovine can produce the polyunsaturated fats

        • linoleic, linolenic (can make DHA from linolenic) and arachidonic acid (from linoleic)

      • milk fat chemistry

        • hydrolysis

          • some bacteria will do hydrolysis of the milk fat

        • oxidation

          • the double bonds and the carbonyl group can be oxidized

    • macrominerals

      • calcium, phosphorus (P), magnesium (Mg), potassium (K), sodium (Na), chlorine (Cl), sulfur (S)

      • health effects of Ca

        • osteoporosis

        • hypertension

        • dental caries

        • cancer

      • trace elements

        • high = iodine (I), manganese (Mn), selenium (Se) chromium (Cr)

        • low = iron (Fe), selenium (Se)

        • regulated (Fe, Cu, Zn) vs unregulated (Se, I)

        • vitamins

    • minerals

      • calcium: functions in the mineralization of bones and teeth, muscle contraction and relaxation, nerve functioning, and blood clotting

      • iron: carries oxygen as part of hemoglobin in blood or myoglobin in muscles, and it is required for cellular energy metabolism

      • magnesium: a factor involved in bone mineralization, the building of protein, enzyme action, normal muscular function, transmission of nerve impulses, proper immune function and maintenance of teeth

      • phosphorus: involved with mineralization of bones and teeth, it is important in genetic material, in cell membranes as phospholipids, in energy transfer, and in buffering systems

      • potassium: facilitates reactions, including the making of protein. it is involved in the maintenance of fluid and electrolyte balance, the support of cell integrity, the transmission of nerve impulses, and the contraction of muscles, including the heart

      • zinc: associated with hormones, it is needed for many enzymes (around 200), it is involved in making genetic material and proteins, immune cell activation, transport of vitamin A, taste perception, wound healing, making of sperm, and normal fetal development

    • mineral constitutes in milk

    • only a third of calcium is free ionized calcium and diffusible

      • typically bound to casein in cows

      • and citric acid in humans

    • in humans the highest is potassium and all of it is diffusible

Lecture 6 1-26: nutritional components in milk pt 2

  • topics

    • composition: proteins, lactose, lipids, minerals, vitamins, enzymes etc.

    • factors affecting composition: species breed, feed, stage of lactation

    • physical and chemical properties: density, freezing point, color, pH, acidity, flavor

    • bacteria

    • somatic cells and microorganisms - lactobacilli, history, significance in cultured products

  • calcium partitioning in bovine milk

    • introduction: milk

      • bovine total calcium 1120 mg/L

        • skim milk (99%)

          • casein is 66%

          • whey is 32%

            • alpha-lactalbumin (.15%)

        • lipid (1%)

      • human total calcium 280 mg/L

        • skim milk (36%)

          • casein 6%

          • whey 29%

            • alpha-lactalbumin (1%)

        • lipid 16-26%

    • sample used

      • sample 1: whole milk from NCSU dairy plant

      • sample 2: skim milk from NCSU plant

      • sample 3: ultracentrifuge skim milk at 100,000 x g for 60 mins

        • supernatant ultrafiltered in centrifuge overnight

        • collect sweet whey using a pipette

        • casein is in a clump at the bottom

      • ultrafiltration of supernatant

        • but it in a filter

        • the top is proteins

        • the bottom is diffusible proteins of the whey

    • procedure: preparation of samples

      • sample 4: centrifuge whole milk at 5,000 x g for 10 minutes

        • chill on ice to solidify fat

        • remove fat with a spatula

        • collect the skim milk fraction by pipette

    • procedure: preparation of samples

      • sample 5: pH of skim milk reduced to 4.6 using 1 N HCl

        • centrifuge at 5,000 x g for 10 min

        • collect acid whey using pipette

        • brings the casein down and forms acid whey

    • calcium values (experimental and literature)

      • the acid displaces the calcium from the micelles, and it goes into the whey fraction

    • calcium distribution in fat, whey, and casein fractions

    • conclusion

      • milk components fractionate in different physical fractions

        • fat

        • cells

        • casein (suspended solids because of negative charge on the outside)

        • whey (water-soluble substances)

      • acid whey contained about one and half times more calcium than sweet whey

  • lactation and diet quality

    • lactations rigorous demands require a mother to intake enough energy and nutrients for maintaining homeostasis and synthesizing nutrient-rich milk for her offspring

    • poor quality diets may lead to poor milk quality and decreased milk yield

    • but diet differences do not always lead to milk composition changes

      human milk calcium concentration varies little amount these countries
  • soluble milk components have multiple chemical forms

    • calcium will interact with anything negative in the milk

    • when calcium binds to something and makes it a neutral molecule it will no longer be soluble

    • citrate is a high in the negative fraction

      • the amount of citrate in the milk effect how much calcium is in the ion state and available for the carbonate fraction

    • by adding CO2 you can change the concentration of carbonate or bicarbonate

      • by changing the pH it will change the ratio of carbonate and bicarbonate

      • higher pH makes more carbonate

        • pulls calcium out and displaces the calcium in the calcium citrate form

      • magnesium and zinc can displace calcium

      • zinc can bind to the casein also

    • we can measure the free calcium, citrate, carbonate and pH to figure out where the calcium is

  • calcium secretion into milk

    • citrate is coming from the mitochondrial energy production and the citric acid cycle

      • TCA cycle

      • citrate is diffusible out of the mammary gland

      • specifically, out of the mitochondria and into the mammary gland in cows

      • in humans we use citrate as a carrier for acetyl CoA for a breakdown of fats in the cytosol

        • the remaining carbon portion of citrate after 2 carbons come off back into the mitochondria

          • cows can because they don’t have the enzyme

            • this is why cows have a higher concentration of citrate in their milk

      • the citrate diffuses into the Golgi apparatus to form casein and lactose

        • forms tiny casein particles in the secretory cells in the mammary

        • the calcium allows the casein molecules to be attracted to each other forming casein micelles

          • dependent on free calcium

  • minor components and micronutrients

    • non-protien nitrogen

      • nucleotides

      • nucleic acids in nucleosomes (particle of nucleic acid inside the cell; once it leaves the cell its called an exosome)

      • urea

      • free AA

    • enzymes

      • lipoprotein lipase

        • breaks down fat in milk

        • if you let milk sit the more free fatty acids there will be

      • lactoperoxidase

      • xanthine oxidase

        • can take unsaturated long chain fatty acid and oxidize them

      • alkaline phosphatase

        • changes the phosphorylation in proteins

        • casein is highly phosphorylated

  • exosomes: found in human milk

    • exosomes are membrane-bound extracellular vesicles (EVs) that are produced in the endosomal compartment of most eukaryotic cells

    • the multivesicular body (MVB) is an endosome with intraluminal vesicles (ILVs) that bud inward into the endosomal lumen. if the MVB fuses with the cell surface (the plasma membrane), these IVLs are released as exosomes

    • exosomes may transfer maternal DNA to the infant

      • could be a form of communication

        • small portion of DNA in a vesicle

  • portion of minerals in milk

    • UHT = ultra-high temperature

      • processing and pasteurization

    • calcium is the highest and the zinc

  • Biological roles for minerals

  • vitamins

    • fat soluble vitamins

      • vitamins A, D, and E

    • water soluble vitamins

      • vitamins C, B1, B2, B6, B12, pantothenic acid (B5), niacin (B3), biotin (B7), folic acid (B9)

    • vitamin concentrations in different species

      • beta-creatine is found in plants and can be converted into vA and enter the fat fraction of the milk

        • making skim milk would significantly decrease vA and vD because the fat fraction is removed

      • if the cow is given hay during winter the dairy producer will add vA

      • also, if the cow is kept indoors then the milk will be deficient in vD

        • vD will be added to the milk

      • vK is needed for blood clotting

        • if low vK it is injected into human babies

      • cows tend to have high B complex vitamins

  • functions of vitamins in milk

    • vA: prevents eye problems, promotes a healthy immune system, is essential for the growth and development of cells, mucous, skin, bone and tooth health, reproduction and immunity

    • vD: strengthens bones because it helps the body absorb bone-building calcium

    • vE: an antioxidant and helps protect cells form damage. it functions in stabilization of cell membranes, support of immune function, protection of polyunsaturated fatty acids, and normal nerve development

    • vC: aka ascorbic acid; needed to form collagen, a tissue that helps to hold cells together. it is an antioxidant, it restores vE to its active form, it helped to synthesize hormones, it supports immune cell function, and helps in absorption of iron

    • thiamin aka B1: part of a coenzyme needed in energy metabolism. it also supports a normal appetite and nervous system function

    • riboflavin aka B2: part of a coenzyme needed in energy metabolism. it also supports normal vision and skin health

    • vB6 aka pyridoxine: part of a coenzyme needed in AA and FA metabolism. it helps to convert tryptophan niacin and to serotonin, and it helps make red blood cells

    • vB12: part of coenzymes needed to make red blood cells, and it important for nerve cell function

    • folate aka B9, folic acid, folacin: part of a coenzyme needed for synthesis of red blood cells. it is also needed to make DNA

    • niacin B3: part of coenzymes needed in energy metabolism. it helps maintain healthy skin and is important for nerve function

    • pantothenic acid: part of a coenzyme needed in energy metabolism

    • biotin: cofactor for several enzymes needed in energy metabolism, fat synthesis, AA metabolism, glycogen synthesis

  • factors affecting composition

    • breed

      • Holsteins make more but less

      • jerseys make more fats, and casein

    • diet and season

    • stage of lactation

  • stages of lactation changes in competition of bovine milk

    • at first the milk is concentrated

      • lower protein and higher fat

      • later is more protein and less fat

      • in colostrum not that much lactose so not that much water and concentrated

      • immunoglobins are high in the whey fraction

        • more whey than casein at first

  • milk fat

    • changes in milk fat characteristics

      • dietary manipulation

        • if you feed cow a lot of polyunsaturated fats then the milk will have a higher concentration of PUFA but it will not change the volume of milk produced

      • seasonal changes

  • seasonal and dietary changed in FA composition of human and bovine milk fat

    • when the person is synthesising fats it will be a short chain like 16:0

    • when the fat is in the diet longer chains are made like 18:1 and 18:2+3

    • cows make more steric acid in the summer

    • cows will have more shorter chain FA in the winter because they are making it not getting it in their diet

  • physical and chemical properties

    • density

      • more or less fat

    • freezing point

      • early or late milk

      • depends on potassium, sodium, and lactase will cause a decrease on freezing point

    • pH

      • the balance between phosphate and sodium and calcium

    • titratable acidity

      • depends on uncharged proteins and inorganic acids

    • flavor

  • density of various fluid dairy products as a function of fats and solids-not-fat composition

    • density decreases as fat increases

  • somatic cells and microorganisms

    • immune and epithelial cells from cow’s body

      • include lymphocytes, macrophages to protect the animal against bacteria

      • the epithelial cells sluff off as the milk is made

        • find the most at the beginning and end of lactation cycle

    • lactobacilli

      • evolved with milk

      • will form lactic acid and cause casein to be protonated

    • history

    • significance in cultured products

      • i.e. cheese and yogurt

  • bacteria

    • pathogenic

      • can cause souring in pasteurization

    • natural flora

    • affect shelf life and milk quality

    • original source of cultured dairy products

  • milk bacteria

    • bacteria in milk were traditionally though as contaminants from the outside as the milk was collected

    • bacteria is actually already there

    • mutualistic milk microorganisms may be dependent on coevolving with their mammalian host to thrive in milk

      • in raw milk some microbes are acid and bile resistant

  • different bacteria from cows’ milk

  • lactation and co-evolution between milk microbiota and mammals

  • diet and gut microbiome

    • diet can play a role on gut microbial diversity in mother and offspring

  • maternal impacts of milk

  • understanding milk microbiota

    • research emphasis on human milk oligosaccharides and its exclusion impacts with offspring development

    • milk of earliest mammals may be vulnerable to microbial proliferation because they were secreted onto skin versus nipples

    • monotreme (platypus and echidna) = lactate of from armpits

    • that protein is known to be antibiotic in the platypus

      • bacteria would thrive in platypus milk

  • major phyla of raw and transgenic goat milk

    • transgenic goats expressing human lysozyme had decreased relative abundance of Actinobacteria compared to wild-type goats by late lactation, but most bacterial phyla were relatively unaffected by this antibiotic

Week 4 January 27

learning objectives

lecture 7 1-31: mammary embryology and comparative anatomy: lactation, milk, and nutrition

  • mammals where did we come from

    • mammals evolved from reptiles

      • one thought was because of the meteorite right outside the Yucatan peninsula (in the Caribbeans) during Paleozoic period

    • looking at the fossil records there was a shift in mammals and reptiles

      • happened between the cretaceous period and the Triassic period

      • though have been a global drop in temp, reduced plant growth, dust in the air

      • the dinosaurs could not regulate their temperature and many survived on plants

  • mammals

    • the classic classification is the lineic structure

    • looks at fossil records and compare it to other animals

      • looks at bone structure

      • and where the soft tissue has to be

    • eutherian mammals give live birth and secrete milk

    • primates are more closely related to bats than rodents

    • Artiodactyla are the 2-hooved animals

      • cows, pigs, camels

    • ruminants related to hippos

  • lactation is a function of mammals (monotremes, marsupial, and eutherian)

    • mammary gland probably evolved form a sweat gland

    • why the abdomen though

      • that’s where the offspring typically sit

    • what other characteristics are unique to mammals that may have influenced the classification of animals

      • hair, live birth in offspring, and inner ear bones, homeotherms, more complex brain function, milk production, one bone in the lower jaw

    • how do mammary structures and functions differ among mammals?

      • number of mammary glands

      • number of openings in the teat canals

      • placement of mammary glands

      • composition of the milk

      • milk storage within the gland to allow once per day or very frequent nursing

      • feeding from the mother creates bonds and induces socialization

    • why can’t a cow get breast cancer

      • a cow’s mammary system is not on its breast but abdomen

  • r-species or k-species

    • r- is large litter, multiple teats and mammary glands, normally don’t have as great of a survival rate, rapid growth

      • i.e. rabbits and mice

    • k- single or twins, have a greater chance of survival, requires more care from mother

      • i.e. elephants and whales

    • fat and protein tend to be high in the rapid reproducing animals and aquatic animals

  • anatomy

  • mammary development in embryo

    • in the mouse at day 10 the tissue will fold on itself

    • by day 12.5 there is a thickening of the cells on the skin forming 2 layers of epithelial cells

    • by day 15.5 a sprout forms

    • by day 18.5 branching happens in different layers: muscle and fat

  • human fetal mammary growth

    • 5 weeks: breast development noticeable in the embryo at 5 weeks of gestation

    • 6 weeks: two milk lines are present, extending from the armpits to the inner thighs

    • 8 weeks: lower milk lines disappear by several weeks

    • 20-32 weeks: upper milk lines develop and form milk ducts by 20-32 weeks gestation

    • 35 weeks: at the end of gestation, duct form openings in the nipples below the skin’s surface

    • 38 weeks: before birth the nipples push outward and become level with skin

  • growth factors establish mammary epithelial and nipple cells

    • PTHrP and BMP signaling mammary bud outgrowth and nipple formation. PTHrP, which is secreted from mammary epithelial cells of the mammary bud, increases BMPR1A expression in the mammary mesenchymal cells (purple), which now responds to BMP4. this triggers epithelial outgrowth, elevates MSX2 expression, and inhibits hair follicle formation within the nipple sheath.

  • human mammary growth and development

    • mammogenesis

      • state of mammary gland from the onset of puberty and throughout pregnancy, when it develops to a functioning state

    • lactogenesis

      • during the last trimester of pregnancy, when milk synthesis and secretion is established

    • galactopoiesis

      • establishment of mature milk and throughout lactation

    • involution

      • occurs at the end of lactation, with the slowly returning to its pre-pregnant state

      • apoptosis when the tissue regresses

  • mouse adult:

    • a schematic of stages (A-F) of mammary gland development in the adult mouse, from pre-puberty through to pregnancy, lactation, and involution

  • mouse mammary growth and development

  • milk producing tissue: alveoli

    • alveoli = alveolus

    • acinus = acini

    • single layer of epithelial cells surrounds the duct aka the mammocyte

    • capillaries also surround the alveoli

    • alveoli cells are called secretory cells

    • milk is held until oxytocin comes along from the pituitary gland

    • causes the myoepithelial to contract

    • also has fat cells = adipocytes

    • and plasma cells for the immune system and antibody production

  • alveoli up close

    • the Golgi apparatus makes secretory vesicles which is the beginning of milk

  • mammary gland anatomy

  • lobules to lobes

  • connective tissue and support

    • the secretory tissue is called the parenchyma

    • the mammary gland has a lot of blood flow

    • dense connective tissue

    • supernumerary teat is an extra abnormal teat

    • lateral suspensory ligament is a belly band, and the median is long wise of the cow

    • if the median ligament degrades in a cow as the get older it will be harder to milk because the teats will go to the side

      • the cow may be culled

  • anatomy of the human breast

    • each breast is an individual exocrine gland that functions and develops independently to extract materials from the blood and convert them into milk

    • each lobe has its own opening through the skin of the nipple

      • lobes are separated by connective tissue

  • advantages of spreading mammary glands

    • allows multiple offspring to nurse at the same time

  • why do we not consume dairy products from mammals that aren’t cows?

    • their lactation cycles it too short

    • the mammary tissue is located in one spot in the cow

      • have a machine that goes all down their body

    • other mammals do not like being milked and will not let down the milk

    • they are not bred to be milked at a parlor

    • in sows to get milk scientist will have to inject them with oxytocin to have a milk let down response

  • udder support system

    • lactating cow: 25kg milk

    • 45kg tissue

    • 70 kg held by suspensory ligament system

  • supportive tissue in the human

    • connective tissue

      • cooper’s ligaments provide a framework to support and attach the breast to the overlying skin and underlying fibrous tissue enclosing the muscles

    • subcutaneous fatty tissues

    • nerves

    • blood and lymph

  • beluga on the go - a litter would be a disadvantage

  • glandular tissue

    • glandular tissue transforms material in the blood and creates nutrients for the milk

    • functional part of the breast that produces and transports milk

    • parenchyma (secretory tissue and lobe)

      • functional parts of the breast

      • composed of smaller individual glands or lobuli

  • areola

    • the pigmented, circular area surrounding the nipple

    • the size and color vary from woman to woman

    • during puberty, menstruation, and pregnancy, it enlarges, and pigmentation increases

    • it partially covers underlying milk ducts

    • acts like the gland cistern with milk storage

  • nipple

    • circular smooth muscle fibers

      • closing mechanism for milk ducts

    • nipple pores

      • the ductule openings at the end of the nipple

  • teat

    • has one duct opening known as the streak canal or teat canal

    • keratin plug is formed to prevent bacteria from entering before the streak canal closes

lecture 8 2-2: mammary embryology and comparative anatomy pt 2: blood, lymph, and nerves, allow milk synthesis and secretion

  • bovine vascular system - arteries

    • the blood supply branches mostly from the dorsal aorta → inguinal canal

    • another branch from the aorta is the cranial epigastric artery which also supplies the mammary tissue

    • the perineal feeds the back

  • bovine vascular system - veins

    • most of the blood goes back through the subcutaneous abdominal vein

    • heart → arteries → arterioles → capillaries → venules → veins → heart

    • high pressure in the artery capillaries

      • forces nutrient into the tissues

  • mammary blood supply in humans

    • most of the blood comes from the subclavian artery

  • bovine lymphatic system

    • is a secondary return system from the mammary gland

      • large enough for bacteria to get through

      • for anything that is too large to flow through the endothelial cell wall

  • human lymph system

    • complex network of capillaries, thin vessels, valves, ducts, nodes, and organs

    • lymph is a thin, yellowish fluid

    • lymph nodes function as filters in the lymph vessels to trap bacteria

    • present throughout the body

    • spleen is connected to the lymph system

  • relationship between lymph, engorgement, and mastitis

    • if inadequate draining pressure will be built up in the breast

    • milk in the ducts → decrease flow of blood and lymph → fluids accumulate (edema) → risk of infection increases → mastitis

    • if you press down the dent will stay because of no blood flow

    • engorgement is the initial milk secretion

  • mammary cytology

    • mammocytes are known as lactocytes

    • engorgement might happen if the myoepithelial is not developed or is not strong enough to push out the milk

    • the lactocytes go from a flat squamous shape to a cuboidal shape as the start to produce proteins

    • the buildup of colostrum can cause engorgements

    • the plasma cells are producing immunoglobins

    • pressure from heart and osmotic pressure of the proteins

    • arteriol- → capillaries → venule out

    • collagen is a supportive tissue around the epithelial cells

    • allows for space when the alveoli expand

    • more pressure make fluid go out

    • which spaces at the cellular level are responsible for swelling and edema during tissue engorgement?

      • Extracellular fluid increases

      • Alveoli may reach capacity storing milk or colostrum

    • what are the tube systems in the breast

      • milk ducts

      • lymphatic system

      • blood, capillary, vascular system

        • responsive to nitric oxide

  • fluid channels

  • therapeutic breast massage in lactation for the management of engorgement, plugged ducts, and mastitis

    • focused gentle massage toward the axillae (near the armpit and is where most of the lymph node are)

    • alternating gentle massage and hand expression

  • nerve supply, what are the functions?

  • nerves on human mammary gland

    • sensory fibers innervate the smooth muscle in the nipples and blood vessels

      • 3rd, 4th,5th, and 6th intercostal nerves

    • extensive innervation of the nipple and areola

      • most comes from the 4th intercostal nerve

      • innervation composed of both autonomic nerves and sensory nerves

  • neuro-endocrine reflex during suckling

    • hypothalamus → PP releases oxy → oxy caused myoepithelial smooth muscle contraction

    • nursing also causes the release of prolactin releasing hormone from the hypothalamus → through portal vein system into the AP → PRH makes the AP release prolactin → prolactin cause milk production and synthesis

    • A primary function of innervation of the mammary gland is to being the milk let down response

  • neuroendocrine reflex

    • capillaries deliver hormones to the alveoli

    • myoepithelial cells contract when exposed to oxytocin

      • squeezing effect on the lobule, forcing milk down the ducts

      • myoepithelial cells multiply and increase in size during pregnancy and lactation

  • mammary gland study

    • understand terms used in the lecture and reading

    • define each in the context of it use and the concept that a term is trying to describe

Lecture 8: mechanisms of milk secretions: introduction

  • History and research tools

    • Palade and pancreatic acinar cells

      • dissolved away all the connective tissues to learn about the mechanism of the pancreas

        • same technique was used for the secretory cells

    • Linzell and Peaker - transplanted goat udder; isolated perfused udder

      • worked at the Hanner institute in Scotland in the 1950s-70s

      • also did perfusion studies

    • Isolated mammary tissue slices

    • isolated acini; grind and find cell distribution

    • electron microscopy

    • cell culture and electrophysiology

  • mouse mammary

  • isolated perfused mammary gland model

    • used to see what is in the secretory glands

    • see what is coming in and out while lactating

    • collects extracellular fluid from the gland

    • infusion pump to add nutrients

    • and oxygen pump

    • will operate a couple of hours after the mammary tissue have been extracted

  • electron microscopy

    • see high resolution of tissues

    • the lipid droplets will end up as holes because they are washed out when the cells are fixed

    • the secretory vesicles get bigger as they get closer to the cell membrane

    • this is happening because of osmotic pressures

      • water will follow the lactose

  • cell culture model system

    • breast tissue (reduction mammoplasty or mastectomy) → chop and digest (collagenase/hyaluronidase) → culture organoids → heterogeneous epithelial cells and fibroblasts (differential trypsinization) → epithelial cells → selection → homogenous epithelial cells → cell senesce

  • bovine mammary epithelial cell cultures for study if mammary gland function

    • cells grow to confluence

    • domes lift off culture dish - tight junctions

    • no 2-d milk syntheis

      • the circle spots in picture d and others are where the cells are not touching the culture plate and are polar

      • this means that the cells are secreting something down and the pressure is pushing the cells up

        • to wish they are making lactose

        • probably secreting ions and the water is following

  • five pathways for milk secretion

    • Golgi/ secretory vesicle pathway

    • lipid secretion

    • eccrine secretions of water and minerals

    • transcytosis

    • paracellular transport

Week 5 February 3

Lecture 9: Milk secretion mechanism

  • name one type of cell contained in mammary tissue that is not a lactocyte, (mammocyte), or mammary epithelial cell:

    • fibroblast, macrophage, lymphocyte, erythrocyte, myoepithelial cell, bacteria

  • isolated perfuesed mamary gland models

    • blood supply is replaced with artificle blood supply

    • have to put in oxygen and nutrients maintain body temperature

    • have to maintain transductor (pressure control)

    • what goes in sample through the arterial port

    • what come out sample through the venous port

    • measure what is captured in the milk

    • operates on the Fick principle

      • the concentration that goes in the profuse fluid x flow in = concentration coming out x flow (the flow is flow of milk + the flow of venous)

robot