Lactation Flashcards
Mammary glands
Highly modified tubuloalveolar apocrine sweat glands Structure: Breast lobe 15-25 compound tubule-acinar glands of variable size Within each lobe: Lobules Multiple acini Terminal ducts Drain each lobule Lactiferous duct Drains terminal ducts Lactiferous sinus A dilation in the duct immediately before the opening Intralobular stroma Hormonally responsive CT, little adipose Interlobular tissue Dense regular CT and adipose tissue
Terminal duct lobular unit (TDLU)
Grapelike cluster of alveoli with terminal ducts and intralobular stroma
Connective tissue
- Loose, collagen rich with dispersed adipose cells
Cells
- Luminal epithelial cells (Columnar to cuboidal)
Myoepithelial cells
-Flattened, basal
Inactive versus active mammary glands
Inactive
Stroma constitute the major portion of lobules
Luminal epithelium columnar, dispersed chromatin
Active
Proliferation of the duct system
Alveoli constitute the major portion of lobules
Luminal epithelium cuboidal, pale cytoplasm, prominent nucleoli
Nipple Parts
Areola, Areolar sebaceous glands, lactiferous ducts, bundles of smooth muscles
Areola
Pigmented skin (melanocytes)
Stratified squamous keratinized epithelium
Dermal papillae
Lactiferous ducts
Transitioning epithelium From the lactiferous duct - Single layer of columnar or cuboidal Within the lactiferous duct - Stratified cuboidal Near duct opening - Stratified squamous keratinized epithelium
Breast cancer
80% are invasive ductal carcinoma
Carcinomas (Arise from epithelium:
Ductal- Within the duct, Lobular- Within the terminal acini)
Sarcomas
- Arise from stroma
In situ
- Has not yet invaded breast tissue, resides inside pre-existing lobules or ducts
Invasive
- Cells infiltrate breast connective tissue
Hormone receptor status
Determines responsiveness to therapeutic interventions
- Estrogen-receptor positive (ER+)
- Human epidermal growth factor expression (HER-2/neu+)
- Progesterone-receptor positive (PR+)
Triple negative
Invasive Breast Cancer: Breast Epithelium
(primarily ductal) Highly mitogenic Hormonally responsive Primarily Estrogen (~75% E+, 65% of E+ are also PR+)
CYP19 aromatase inhibitor
Inhibits peripheral conversion: androgen –> estrogen
(postmenopausal)
Selective Estrogen Receptor Modulator (SERM)
(E.g.: Tamoxifen, agonist at bone and uterus; antagonist at breast)
(premenopausal)
Estrogens/Progesterone
Fetoplacental production
Mammogenic
Continue to rise throughout pregnancy
Prolactin (PRL)
Secreted by anterior pituitary gland during pregnancy
Mammogenic, lactogenic
↑ 10-20x from ~ 5th week until parturition
Estrogen stimulates production & inhibits action
Human chorionic somatomammotropin (hCS)/ Human placental lactogen (hPL)
- Structurally similar to PRL and GH
- Produced by the placenta
- Lactogenic
State of lactation hormones near end of pregnancy
Near end of pregnancy:
breasts are fully developed but milk production is suppressed except for small amount of colostrum
- Inhibited by high estrogen & progesterone during pregnancy
Oxytocin
Neurohypophyseal hormone
Produced during parturition
Stimulates uterine contractions
Promotes contraction of myoepithelial cells resulting in milk ejection (“let-down”)
↑ oxytocin synthesis and release via positive feedback caused by suckling, anticipation of nursing, and audiovisual stimuli
Four Stages of Lactation
Milk Synthesis
Initiated by PRL and hPL in later pregnancy
- Lactogenesis
Milk synthesis by alveolar cells and secretion into alveolar lumen
Initiated after birth by the loss of placental steroids - Galactopoiesis
Maintenance of established lactation
Mainly controlled by PRL which is increased by infant suckling - Milk Ejection
Passage of milk to the duct system, collection in ampulla and larger ducts, and delivery to infant
Controlled by oxytocin release stimulated by suckling, anticipation of nursing, and audiovisual stimuli
Initiation of Lactation
Requires coordinated action of several stimuli:
↑ Prolactin
- Mammogenic, lactogenic, galactopoietic
↓ Estrogen and Progesterone
- High estrogen & progesterone inhibit onset of lactogenesis
- Abruptly fall following parturition
↑ Oxytocin
- Galactokinetic
Suckling
- Inhibits hypothalamic dopaminergic neurons
- Primary neural stimulus post-parturition
Lactation Following Parturition
After birth, estrogen and progesterone levels drop and milk is produced in 1-7 days
Colostrum: special fluid few hours of nursing
- high in nutrients, fats, and antibodies to protect the newborn from infection
After initiation of lactation, amount of milk produced is mainly controlled by prolactin (galactopoietic)
- Produced in response to the suckling of the infant
- Neurohumoral reflex leads to burst of PRL secretion
PRL levels return to normal after a few weeks if no breast-feeding occurs
With continued breast-feeding, PRL levels maintain at a higher baseline level than in non-pregnant females
Milk Ejection
Alveolar milk accumulates in the lactiferous sinuses or ampullae (enlargements of ducts near opening of nipple)
Suckling:
↑ hypothalamic release of oxytocin from posterior pituitary
Oxytocin:
↑ contraction of myoepithelial cells around the ducts
Negative maternal emotions (frustration, anger, anxiety) can inhibit oxytocin secretion & suppress milk ejection reflex
Effects of Suckling on Hormone Release Maintaining Lactation and Milk Ejection
Suckling stimulus
Activates afferent neural pathway. Breast –> spinal cord –> hypothalamus
- Inhibition of Inhibition
Inhibition of Dopamine (Prolactin Inhibitory Factor, PIF) from the hypothalamus
Removes inhibition of lactotrophs –> ↑prolactin –> milk production
Stimulates hypothalamic oxytocin production & release from posterior pituitary
Activates receptors on breast myoepithelial cells –> milk “let-down”
- Inhibits hypothalamic production of GnRH
Results in ↓ LH and FSH, inhibition of ovarian cycle
Compositional Differences in Milk
Colostrum: thin, yellowish milk-like substance secreted first few days after parturition. High concentration of immunoglobulins.
Human milk: emulsion of fats in an aqueous solution containing sugar (lactose), proteins (lactalbumin and casein), and K+, Ca2+ , Na+, Cl- and phosphate.
Cow’s milk: nearly three times more protein than human milk due to high casein content and higher electrolyte concentration.
Immunology and breastfeeding
Infant immune system is immature at birth
In utero, transfer of antibodies across placenta
Protection tapers off quickly after birth
Breast milk contains a number of different agents to protect the infant:
Secretory IgA
WBCs: neutrophils and macrophages
Growth factors: EGF (epidermal growth factor), NFG (nerve growth factor), IGF (insulin-like growth factor)
Benefits of Breast Feeding
Infant
Reduction in infections Secretory IgA Initial increased growth Decreased obesity in adulthood Positive effects on mental development
Mother
More rapid and sustained weight loss
Lactational amenorrhea
Psychological benefits
Cost effective
