Physiology of lactation

lactation

1. PHYSIOLOGY OF LACTATION PRESENTER: DR VARSHA V. HIRANI FACILITATOR: PROF. MUSOKE

2. OBJECTIVES: Understand the structure of the breast D escribe the stages of lactation Composition of breast milk Factors affecting lactation Medications that affect lactation 2

3. Definition of lactation Lactation describes the production of breast milk and its secretion from the mammary gland after delivery 3

4. Structure of the breast Parenchyma consists of 10-15 ducts extending from the nipple to terminate in grape-like clusters known as alveoli (basic unit) via ductules from lobules There are 15-20 pyramid shaped lobes separated by cooper ligament and each contains lobules which are further separated by fat and connective tissue( stroma ) Nipple surrounded by area of hyperpigmented skin – areola 4

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6. Physiology of Lactation. Lactation can be divided into 5 stages: Mammogenesis -Development of breasts to a functional state Lactogenesis -Synthesis and secretion of milk from the breast alveoli Galactokinesis -Ejection of milk outside the breast Galactopoiesis -Maintenance of lactation Involution -regression and atrophy post lactation 6

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8. 1.Mammogenesis Growth of ducts and lobuloalveolar systems This starts from birth to puberty and continues in pregnancy Ductal sprouting predominates in 1 st trimester and lobular sprouting occurs more in 2 nd trimester hence the breast will contain more glandular epithelial cells than stroma Just before and during parturition there is a new wave of mitotic activity causing growth growth and maturation 8

9. Hormonal influence during mammogenesis Prepubertal growth- depends on estrogen and progesterone. Secretion of prolactin and somatotropin by the pituatory gland results in mammary growth. Adrenocorticotrophic hormone(ACTH) and thyroid stimulating hormone(TSH) acting on the adrenal gland and thyroid gland also play a minor role in growth of the mammary gland 9

10. 10 Pubertal growth - When the hypophyseal-ovarian –uterine cycle is established, there is extensive branching of the duct system and parenchymal proliferation and canalization of the lobuloalveolar units controlled by estrogen and progesterone Hormonal influence during mammogenesis…

11. 11 During pregnancy In early pregnancy a marked increase in ductular sprouting, branching and lobular formation is evoked by luteal and placental hormones. Progesterone :causes increased growth of alveoli size and lobes, Estrogen :Stimulates milk duct system to grow and differentiate, deposition of fat. Prolactin :contributes to increased growth and differentiation of the alveoli and ductal structures

12. Types of lobules Type 1- (virginal lobule) when an average of 11 alveolar buds/ductules cluster around a terminal duct, this is apparent within 1 to 2 years after onset ofmenses Type 2 - changing levels of estrogen and progesteron during menstrual cycle stimulates type 1 lobules to sprout new alveolar buds and evolve to mature structures, type 2-47 lobules Type 3 - in pregnancy, 80 lobules Type 4- attained in late pregnancy with breast milk 12

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14. 2. LACTOGENESIS(stage 1) Stage 1: occurs in mid pregnancy There is initiation of milk synthesis, alveoli differentiates into secretory cells and prolactin stimulates mammary secretory cells to produce milk. insulin and serum growth factor induced cell division of stem cells of the gland and presence of cortisol for formation of alveoli is required for induction of milk synthesis . Further differentiation is inhibited by high levels of progesterone from the placenta and loss of progesterone receptors in the lactating breast 14

15. Prolactin: exerts its effects through receptors for initiation of milk secretion located on the alveolar surfaces . stabilizes and promotes transcription of mRNA and stimulates synthesis of lactoalbumin, which is a regulatory protein of the lactose synthetase enzyme system Increases lipoprotein activity in the mammary gland In conjunction with estrogen and progetserone it attracts and retain Ig-A immunoblasts estrogen enhances prolactin production by 10-20 fold. This is regulated by human placental lactogen which has an inhibitory effect Its inhibited by prolactin inhibiting factor under control of catecholamines in the hypothalamus . 15

16. LACTOGENESIS-stage 2 Stage 2: from late pregnancy to day 8. This is triggered by rapid drop in progesterone levels after placental delivery requires the presence of elevated levels of prolactin and cortisol , insulin , growth hormone and parathyroid hormone to facilitate mobilization of nutrients and minerals there is a switch from endocrine to autocrine control 16

17. 2. Lactogenesis. Pathways for milk secretion by the mammary epithelial cell I - Exocytosis : milk protein and lactose are transported in Golgi-derived secretory vesicles, with water and electrolytes in to the alveolar lumen II – Reverse Pinocytosis : lipid formed in smooth ER forms droplets and covered by phospholipid membrane transported as milk-fat globule III – Apical transport : Direct movement of monovalent ions, water, and glucose across the apical membrane of the cell. 17

18. Lactogenesis…… IV – Transcytosis . sodium, potassium, chlorides, some monosaccharides, and water V - The paracellular pathway for some interstitial fluid components and leukocytes to pass by diapedesis through the tight junctions. 18

19. Pathways for milk secretion by the mammary epithelial cell Exocytosis Reverse pinocytosis Apical transport Transcytosis Paracellular pathways 19

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21. galactokinesis Depends on the suckling mechanism of the baby and the contractile action which will express milk from the alveoli into the ducts. This contraction is brought about by the action of Oxytocin Milk let down reflex/milk ejection reflex Inhibited by psychic condition /pain /breast engorgement 21

22. oxytocin: Released from posterior lobe of the pituatory gland during nipple stimulation or sensory stimulation( visual, tactile , olfactory or auditary) Causes ejection of milk from the alveoli gland by contraction of the myoepithelial cells into ductules and ducts 22

23. Ascending impulses from the nipple and areola thoracic sensory (4, 5 and 6) afferent neural arc paraventricular and supra optic nuclei of the hypothalamus Oxytocin from the posterior pituitary produces contraction of the myoepithelial cells of the alveoli and the ducts containing milk. ("milk ejection" or "milk let down" reflex) Milk is forced down into the ampulla of lactiferous ducts, wherefrom it can be expressed by the mother or sucked by The baby. This occurs between 30sec. to 60sec. During suckling, a conditioned reflex is set up: 23

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25. Galactopoiesis. Prolactin is the hormone for maintenance of lactation And suckling is essential for maintenance of milk secretion Periodic breast feeding relieves pressure in the ducts and promotes more secretion Controlled by autocrine system(supply-demand) 25

26. 5. Involution Apoptotic cell death and tissue remodelling post lactation Requires a combination of lactogenic hormone deprivation and local signals to undergo regression and atrophy 26

27. 27 Variations in composition : Colostrum(1-5 days) – is reacher in proteins ,minerals, immunoglobulins , anti inflammatory factors(PGE1 and PGE2, cytokines), phagocytes and lymphocytes. Mature milk(>30 days )-larger quantity than colostrum, Foremilk –thin, proteins, lactose, water and other nutrients. Hindmilk –more fat therefore whiter, provides much of the energy of a feed. Other components include human growth factors, cortisol, insulin, thyroxine and prolactin

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29. FACTORS AFFECTING LACTATION Maternal problems : stress(post c/s,stressful vaginal delivery or other psychosocial stresses) opiates and beta-endorphins are released that block the stimulus-secretion coupling thus reducing oxytocin release polycystic ovarian syndrome, theca lutein cysts, obesity, labour analgesia, dm type 1, placental retention-increased circulating progesterone Alcohol dependence 11/4/2014 3:33 PM 29

30. FACTORS AFFECTING LACTATION.. Infrequent suckling/failure to empty breast causes Elevated intrammary pressure also disrupts connections between cells and their attachment to the basement membrane disrupting synthesis and secretion of milk components. Premature infants -prolactin may not be sufficient 30

31. MEDICATIONS AND LACTATION Medications that increase lactation- metoclopramide domperidone phenothiazine neuroleptics -chlorpromazine risperine Hypoglycemics H2 antagonists-cimetidine Antihypertensives-methyl dopa, b blockers 31

32. MEDICATIONS AND LACTATION Medications that reduce lactation- Bromocryptine(dopamine agonist) Progesterone,estrogen-OCP Clomiphene citrate ergotamine pseudoephedrine(in cough syrups) Pyridoxine Prostaglandins- PGE/F2alpha Levodopa/carbidopa 32

33. Advise to the mother to improve lactation Good health; Early and sufficient treatment of illnesses; Proper balance between rest and exercise; Freedom from worry Care of the breast /nipples during pregnancy Post natally frequent breast feeding Avoid breast engorgement Plenty of fluids Adequate nutrition. 33

34. Thank you !

35. ANY QUESTIONS? 35

36. References E-medicine – Human milk and lactation. Breastfeeding and human lactation-Jones and Bartlett Series. Breast feeding, guide for medical proffesion by Ruth Lawrence.