_HD-201_-E01_T03_Histology-of-Mammary-Glands_compressed

Mammary Glands

• Develop embryologically from surface ectoderm invaginations along the milk lines from the axillae to the groin.
• They are located in the anterior chest wall.
• Exocrine glands that produce milk to nourish young offspring.
• Considered compound tubuloalveolar glands.
• Histologic picture varies based on sex, age, and physiologic status.

Structural Features

• Composed of 15-25 lobes of compound tubulo-alveolar types, each separated by dense connective and adipose tissue.
• Breast size varies among women, depending on the volume of adipose tissue rather than epithelial or ductal components.
• Each lobe contains several ducts that open into a terminal secretory lactiferous duct (2-4.5 cm long).
• These ducts open into the nipple, which has 15-25 pore-like openings, each about 0.5mm in diameter.
• Areola: the darkly pigmented area around the nipple, containing sebaceous glands and abundant sensory nerves, is continuous with the mucosa of the lactiferous sinuses.
• Lactiferous sinus: widening of the lactiferous duct.

Mammary Duct System

• Consists of lobes containing alveoli or acini and their excretory ducts.
• Acini are surrounded by intralobular loose connective tissue.
• Denser collagenous interlobular connective tissue surrounds the larger ducts and lobules.
• Milk secretion pathway:
  • Milk secreted by epithelial cells lining the alveoli.
  • Excreted into intralobular ducts, then interlobular ducts.
  • Interlobular ducts continue as lactiferous ducts opening into the nipple.

Changes in Mammary Glands

• Reach greatest development around age 20.
• Atrophic changes begin around age 40 and become marked after menopause.
• Menstrual cycle: cause physiologic changes and changes in size with menstruation symptoms.
• Pregnancy and lactation: cause the most striking changes in size and functional activity.

Resting Mammary Gland

• Description: mammary gland at birth and until before pregnancy.
• Stage: Birth
  • Characteristics: devoid of acini and consists of only short branching ducts.
• Stage: Puberty
  • Characteristics: increased branching of ducts due to rising ovarian hormone levels and small masses of epithelial cells forming at the ends of the smallest branches.
• Stage: Adult
  • Characteristics: minimal cyclic changes in glandular tissues, slight increase in breast size and fullness mid-cycle due to increased blood flow and edema, and less nodular breast tissue from day 8-14.

Active Mammary Gland

• Referred to as "Functional State "
• Occurs during pregnancy due to breast growth:
  • Estrogen
  • Progesterone
  • Prolactin: promotes the growth of mammary alveoli.
• Milk production prevented due to the estrogenic and progesterone rich environment.
• Elevated levels of estrogen and progesterone prepare for lactation.
• Rapid growth and proliferation of the duct system.
• Decreased growth of adipose and connective tissue.
• Development of acini.
• Increase in plasma cells, lymphocytes, and eosinophils.
• Expansion of spherical masses of cells, lumen development, and differentiation into acini.

Myoepithelial Cells

• Surround the acini and ducts
• Stellate-shaped cells forming a basket-like network around the acini.
• Arranged along ducts and between the basal lamina and epithelial cells lining alveoli.
• Milk-ejection/Let-down reflex: stimulation of the nipple by a suckling baby results in oxytocin release from the pituitary gland, causing the myoepithelial cells to contract and express milk.
• Negative emotional stimuli can inhibit the liberation of oxytocin and prevent the reflex.
• Regulate growth and morphogenesis of alveoli.
• Role in information exchange between luminal cells and extracellular matrix.
• Suppress breast cancer by limiting the growth and mobility of cancer cells.

Lactating Mammary Glands

• Seen in breastfeeding mothers.
• Increase in alveoli filled with milk secretion and lined by cuboidal active secretory cells.
• Reduced interlobular connective tissue into thin strips, giving room to the increased volume of alveoli.
• Appearance of different regions varies depending on functional status.

Mammary Gland Development

• Menopause: breast reverts back to the pre-pubertal stage and has reduced size and loss of shape, leading to sagging.

Breast Milk Composition

• Water and electrolytes: >80%
• Carbohydrates: 7%, accounting for 40% of total calories, primarily lactose, promoting healthy gut bacteria, insulin regulation, and the growth of gut antimicrobial factors, synthesized in the Golgi apparatus and secreted with lactalbumin, generating the osmotic gradient that draws water and Ca2+ into the alveolar lumen.
• Lipids: 4%, for brain development and absorption of fat-soluble vitamins.
• Protein: 0.9%, whey (60%) and casein (40%), easily digested.
• Immunoglobulins (IgE and IgA): protect infants from bacterial and viral infections.

Colostrum

• First milk produced, containing high levels of proteins, minerals, and immunoglobulins.
• Provides passive immunity to the breastfed baby.

Human vs Cow's Milk

• Carbohydrate, protein, and fat content depend on the species's nutritional requirements.
• Protein content in cow's milk is more than double that of human milk
• Fat: Similar values of total fat content between human and cow's milk
• Calcium: Higher calcium is needed in calves, since they grow more quickly than humans and have larger skeletons, especially in females
• Iron: Cow's milk contains little iron, which is why it is not suitable for infants under the age of 12 months
• Higher whey protein content in human milk makes it easier for babies to digest

Milk Secretion

• Lipid Component: apocrine secretion where triacylglycerols synthesized in the rough endoplasmic reticulum are released into the cytoplasm and fuse into larger droplets that bud off with a part of the plasmalemma.
• Carbohydrates and Milk Protein: merocrine secretion where milk proteins synthesized in the endoplasmic reticulum and lactose synthesized in the Golgi apparatus accumulate in vesicles that fuse with the apical plasma membrane and are discharged.

Clinical Significance: Lactational Amenorrhea

• Temporary, natural family planning method effective for up to 6 months if:
  • Infant is fully breastfed every four hours during the day and every 6 hours at night.
  • Infant is less than 6 months old.
  • Woman has not had a period or bleeding after 56 days postpartum.
• Mechanism: infant breastfeeds, hypothalamic GnRH decreases, pituitary LH and FSH decrease, and ovarian follicle stimulation doesn't occur.

Weaning

• Stopping breastfeeding leads to loss of prolactin and involution of breast tissue.
• Alveoli degenerate, epithelial cells undergo apoptosis, and macrophages remove dead cells and debris.
• Breast size decreases or returns to its pre-pregnancy state.

Male Mammary Glands

• Develop similarly from birth to puberty.
• Testosterone inhibits the growth, may have gland proliferation in males (gynecomastia).
• Rudimentary duct system, little postnatal development, duct system may respond to hormonal stimulation.

Breast Cancer

• Neoplastic cells invade surrounding stroma forming a palpable mass.
• Curable through mammogram and ultrasound screening.
• Screening:
  • Begin as early as 40.
  • If a first-degree relative has breast cancer: begin by their age of diagnosis minus 10.
  • Ultrasound gives better imaging of masses.
  • MRI for post-breast augmentation.
  • Ultrasound preferred for dense mammary glands.