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Karen Gibson

Breast

4BGDBPhysiology2.png

  • Breast consists of glandular tissue arranged in lobes, which consist of alveoli (acini) that produce milk and drain into lactiferous ducts which exit the breast at the nipple or areola.
  • There is also fat in the breast and suspensory ligaments (which sag in age)
  • This breast is well developed (someone late in pregnancy)

Development of breast

Development of breast through reproductive life
  • Before puberty, there isn't much to breast except ducts
  • Non pregnant adult female, it has mature ducts and some alveoli
  • In pregnancy, oestrogen acts to stimulate duct development. Progesterone and PRL (prolactin) assist with alveoli. hPL is also needed
    • Alveoli drain into lobules, which make up lobes (15-20 lobes in a breast)
    • In non pregnant female adult there is small variation in breast during the cycle
  • Lactating breast
    • Alveoli distended with milk
    • Depends on PRL and a drop in estrogen and progesterone. Oxytocin is needed for milk ejection

Terminology

  • Mammogenesis - Differentiation and growth of mammary glands
    • Mammogenesis happens in puberty/pregnancy
  • Lactogenesis - Initiation of milk production
    • Lactogenesis occurs after pregnancy
  • Galactopoiesis - Maintenance of milk production
    • Involves:
      1. Milk secretion
      2. Milk ejection

Note that you need both milk secretion and milk ejection (if you stop ejecting it, you'll stop secreting it)

Mammogenesis

  • During pregnancy
    • fat tissue in breast replaced
    • ductular-lobular-alveolar growth.
      • prominent lobules form
      • branching of the duct system
      • lumina of alveoli dilate
      • alveolar cells differentiate (note these cells have prolactin receptors)
    • influence of estrogen, progesterone, prolactin, human placental lactogen, insulin, adrenal steroids.

Lactogenesis

  • The initiation of milk production
  • Depends on
    • presence of high levels of prolactin
    • withdrawal of estrogen and progesterone

(Note: alveoli are sufficiently differentiated to begin milk secretion by 4 months of pregnancy; breasts not responsive to prolactin until after parturition)

  • After parturition, prolactin levels fall, but more slowly.
  • In the absence of suckling, milk secretion will last (if scantily) for 3-4 weeks.

Graph of pregnancy hormones

4BGDBPhysiology4.png

  • During pregnancy, oestrogen and progesteron rises
  • Prolactin also rises (from AP of mother)
  • High oestrogen levels of mother stimulate AP to make prolactin (more lactotrophs and more transcription of prolactin gene)
  • After birth (once placenta is delivered), there is a huge drop in E and P and also in hPL. By contrast, PRL doesn't drop as much (maintained by AP -- although it is falling slowly)
  • During this stage the milk initiation starts
    • C - colostrum
    • T - transitional
    • M - mature (maintained until weaning - cessation of feeding from breast)
  • It is critical that the baby does suckle or this milk production will stop after 3-4 weeks

Galactopoeisis - milk secretion

Prolactin level changes due to suckling at different times postpartum
  • Milk secretion
    • synthesis of milk constituents within alveolar cell.
    • Intracellular transport of constituents
    • discharge of constituents from cell into alveolar lumen
  • Depends on the continued secretion of prolactin from the anterior pituitary.
  • Prolactin release stimulated by suckling.
  • The baby orders its next feed during the current one.
  • Ensure supply reaches demand - treatment for low milk production: put the baby to the breast very often

Note: babies suckle >3 times per day

  • Graph
    • Don't need as much PRL to have an effect once you've been lactating for a while (structures are in place etc, becomes more sensitive)

Suckling and prolactin

  1. Suckling
  2. Sensory nerves
  3. Synapse in spinal cord
  4. Neurons to hypothalamus
  5. Arcuate nucleus
  6. Inhibits dopamine release
  7. Removes inhibition on lactotrophs in anterior pituitary
  8. Prolactin release
  9. Breast
  • Normally the arcuate nucleus of the hypothalamus produces dopamine that inhibits PRL, but suckling inhibits the dopamine (so PRL is released, which goes to the breast)
  • To inhibit lactation, you can give a dopamine agonist

Effects of prolactin

  • Stimulates uptake of some amino acids.
  • Induces transcription of genes for the milk proteins casein, lactalbumin and β-lactoglobulin.
  • Induces enzymes necessary for the synthesis of lactose (galactosyltransferase and N- acetyllactosamine).
  • Stimulates synthesis of fatty acids and phospholipids.
  • Upregulates its own receptors.

Assists every step in the process of milk production (takes care of the protein, carbohydrate and fat in turn, then upregulates its own receptors - see the dot points above).

Galactoporesis - milk removal

Myoepithelial cells surrounding alveolus
  • Milk removal
    • passive removal of milk from cisterns and large ducts.
    • ejection of milk from alveoli (“let down” or “draught”)
  • Oxytocin stimulates contraction of the myoepithelial cells which surround each alveolus, forcing milk out of the alveoli into the small lactiferous ducts.
  • Build up of intramammary pressure results in milk “letdown” causing milk to spurt from the nipple.
  • Milk ejection reflex
    • Suckling --> neuroendocrine reflex --> oxytocin release.

Oxytocin not only contracts smooth muscle in the uterus, but also in the breast. There are myoepithelial cells wrapped around the lactiferous alveoli - squeezing these alveoli and forcing the milk into the ducts (causes letdown, where the milk spurts from the nipple). It is neuroendocrine reflex (like PRL release)

Suckling and oxytocin

  1. Suckling
  2. Sensory nerves
  3. Synapse in spinal cord
  4. Neurons to hypothalamus
  5. Paraventricular and supraoptic nuclei
  6. Stimulates production of oxytocin
  7. Oxytocin release from posterior pituitary
  8. Breast
  9. Contraction of myoepithelial cells
  • Similar reflex to prolactin, but this time uses the paraventricular and supraoptic nuclei of the hypothalamus

Not just suckling --> oxytocin

  • The reflex can also be conditioned to occur in response to other stimuli (baby’s hungry cry, rattle of milk bucket).
  • The reflex is particularly susceptible to inhibition by physical and psychological stresses.
    • ? Due to adrenaline, activation of SNS, inhibition of oxytocin release.
    • important to consider while lactation being established. Need calm mother, reassurance etc.
  • Doesn't just respond to suckling, but also to baby's cry etc
  • Anxiety causes high levels of adrenaline, which inhibits oxytocin release and inhibits letdown

Suckling - not sucking

Internal view of suckling
  • The infant expresses the milk.
  • The nipple and areolar are drawn out to form a teat which is compressed between the infant’s tongue and hard palate.
  • Relief of pressure allows rapid refill.

The infant's don't actually suck the milk out. Quite a large proportion of the nipple and areola are drawn into the mouth of the baby. The baby squishes the nipple/areola between its tongue and the hard palate, so it fills and then swallows (doesn't suck).

Lactation also inhibits the ovarian cycle

  1. Suckling
  2. Sensory nerves
  3. Synapse in spinal cord
  4. Neurons to hypothalamus
  5. Arcuate nucleus and preoptic area
  6. Fall in GnRH production (fall in GnRH production is also stimulated by increased prolactin)
  7. Inhibition of FSH and LH release
  8. Inhibition of ovulation
  • Not only do you get increase in prolactin, but you also get a fall in GnRH. Both of these mean less FSH and LH, inhibiting ovulation (even having high prolactin stops ovulation). Abnormally high prolactin outside of weaning etc can cause infertility.

Contraceptive effect of lactation

  • Lactational amenorrhea - is not a reliable source of contraception (particularly if mother is well-nourished and particularly if the child has started on solid foods and is suckling less)
  • No lactation after delivery --> ovulatory cycles resume in 8-10 weeks (range up to 18 weeks).
  • But, even if lactating, ovulatory cycles eventually resume
    • Especially in well nourished women
    • Especially once solids introduced --> decreased suckling
  • In Bangladesh, anovulation averages 18-24 months

Composition of milk varies

  • Colostrum - first week
    • yellow, sticky
    • contains less water-soluble vitamins (B, C) fat and lactose than mature milk
    • contains more protein, more of some minerals, fat soluble vitamins (A, D, E, K) and immunoglobulins.
    • Low volume
  • Transitional phase (1-3 weeks)
  • Mature milk
    • also variation between foremilk and hindmilk
      • Varies in composition - the foremilk (start of drink) is more watery, hindmilk (end of drink) has much more fat. Therefore during hot weather, the baby is drinking a lot more often, it's mainly getting water (the foremilk relieves thirst, the hindmilk relieves hunger)

Contents of human mature milk

  • Water (90 g%)
  • Lactose (7 g%)
    • Promotes intestinal growth of Lactobacillus bifidus flora
    • Galactose essential for myelin formation in nervous tissue
  • Fat - including essential fatty acids, saturated fatty acids, unsaturated fatty acids
    • Main energy source
    • Almost completely digestible (well-emulsified, small fat globules)

Lots of water in milk, women often drink from a water bottle during feeding.

  • Main protein in human's milk is lactalbumin and lactoglobulin (easier to digest than casein for baby - therefore it's not recommended to give them cow's milk, which also has too many minerals)
  • Amino acids - including essential amino acids
  • Protein - including lactalbumin, lactoglobulin.
    • Casein is 44% of total protein in human milk; 82% in cow’s milk.
  • Minerals - including calcium, iron, magnesium, potassium, sodium, phosphorus, sulphur
  • Vitamins - including A, B1, B2, B12, C, D, E, K.
  • pH 7.0.
  • Energy value ~ 70 kcal/100 ml.
  • Cells (macrophages, neutrophils, lymphocytes)
    • Colostrum - 7-8 x 10^6/100ml; mature milk - 1-2 x 10^6/ 100 ml

Breastfeeding association

  • Laypeople who are keen on breastfeeding, form support groups.
  • Babies aren't born knowing how to breastfeed and the mother doesn't instinctively know either
  • Breast pumps allow you to get milk even if you're not going to be with the baby for a while and you still want to feed them with it (e.g. express the milk and then someone else can feed it to them later).

Other person

Objectives

  • Overview of infant formulae
  • Specialised paediatric formulae
  • New developments

Reasons people don't breastfeed

  • Breastfeeding is the preferred way to feed a baby.

However, not all mothers want to breast feed – or unable to breast feed

  • Common reasons not to breast feed
    • Previous difficulties breast feeding - Nipple anomalies, Embarrassment , Anxiety, Stress, Smoking, Illness
    • Possible risks with BF – exclusive breast feeding for >6 months --> Fe deficiency, mother who is strict vegan or vegetarian will need to monitor her own diet for risks of iron, Vit B12, folate deficiency

Formulae regulation

  • WHO - International Code – 1981
  • MAIF (Marketing in Australia of Infant Formulas)
    • Voluntary Clauses
  • FSANZ
    • Food Standards Code 2.9.1 Regulates:
      • Quality
      • Composition &
      • Labelling of infant formulas

Infant formulae on the market

In the supermarket, it is difficult for parents to choose a type of formula, because there are so many on the market. BGDBFormulas1.png

Note: "Gold" just means that it contains essential fatty acids.

Types of infant formulae

  • Standard infant formulae
  • Progress/follow-on/toddler formulae
  • Low birth weight formulae
  • Pre term formulae
  • Specialised infant formulae

Nutritional composition of formula (per litre)

Know roughly the compositions of human milk, formula and cow's milk (Follow on formula does virtually the same thing as normal formula) BGDBFormulas2.png

Preterm and low birth weight infants

  • Increased growth rate and high metabolic needs
  • Inadequate nutrient stores
  • Immature physiological systems –respiratory, digestive and renal

LBW formulas compared to a standard infant formula:

  • 20% more Energy
  • 50% more Protein
  • Additional Vitamins & Minerals – Na, K, P, Mg

Human Milk Fortifier (HMF) – may be used to supplement breast milk, not added to infant formula

Note: at term, remember to swap the milk over in the case of a preterm baby

Specialised formulae

  • Macronutrient modification
    • protein
    • carbohydrate
    • fat
    • micronutrient
  • Medical condition dependent
  • Expensive & PBS - government pays for most of formula (to help out families who can't afford the needed formula)
  • Supervised by paediatrician or paediatric dietitian

Protein modified formula

  • Is formula containing hydrolysed, not intact protein

BGDBFormulas3.png

Notes:

  • Put a child on a partially hydrolysed formula to reduce the risk of allergy
  • LCP = long chain polyunsaturated fatty acid (the same as Gold that's on the market)

Carbohydrate modified formula

BGDBFormulas4.png

Notes:

  • Lactase deficiency is the same as lactose intolerance

Fat modified formula

BGDBFormulas5.png

Notes:

  • LCT = long chain triglyceride
  • MCT = medium chain triglyceride

Other specialised formulae

BGDBFormulas6.png

Notes:

  • This slide is unlikely to be examined

Nucleotides

  • Conditionally essential nutrients
  • Serve as nucleic acid precursors and act as

inter- and intracellular biological mediators

  • Exogenous supply may be beneficial in infancy
  • Animal trials demonstrate enhanced indices of humoral and cellular immunity and improved survival rates following infection with pathogens
  • Results from human studies are not consistent
  • More study into the effect of NT supplementation on immunity is required.

Notes:

  • Nucleotides are a new addition to formulas
  • Breast is best!

Long chain PUFAs

  • DHA (22:6n-3) and AA (20:4n-6)
  • ? Conversion of EFAs (ALA and LA) in vivo
  • Added to infant formula with the aim of improving growth, visual acuity and brain development
  • n-3 LC PUFAs are potentially strong anti-inflammatory agents
  • Proper balance between n-3 and n-6 must be maintained
  • More research is required to determine specific benefits and safety

Alpha-lactalbumin

  • Major protein found in whey
  • A source of essential amino acids (especially cysteine and tryptophan)
    • whey:casein is normally 60:40 (usually whey dominant)
  • Different AA profiles between cow’s milk and human milk mean that formula has a higher protein concentration
  • New technology- formulas can be made with lower protein concentration but higher tryptophan concentrations

Prebiotics

  • Prebiotic-Nondigestible substances that provide a beneficial physiological effect for the host by selectively stimulating the favourable growth or activity of a limited number of indigenous bacteria
  • Does not raise safety concerns with regard to growth & adverse affects
  • Clinical effects & safety of one prebiotic product should not be extrapolated to other prebiotics
  • Some Evidence is associated with some clinical effects such as increased stool frequency & stool softening
  • Lack of data on the long term effects of prebiotics
  • ? Routine use of prebiotics in infant formulae

Probiotics

  • Probiotic-Live, microbial food ingredients thought to be beneficial to health
  • Modulate the immune system
  • Benefits:
    • Reduce the severity of acute diarrhoea
    • Benefit NEC (necrotizing enterocollitis)
    • Benefit: C. difficile infections
  • Not all probiotics are similarly effective
  • Not indicated for immunocompromised (malnourished or ill) neonates
  • Long term effects have not yet been studied in detail

What else to think of when using an infant formula?

  • Preparation
  • Hygiene
  • Cost
  • Dilution

Infant formulas are pretty much the same (despite cost). Try to get breast feeding, but if they won't, then just get any formula. Dilution - if too watery, they'll fail to thrive.