Lactation – All About I Have To Know

Lactation – All About I Have To Know

Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all post-pregnancy female mammals, although it may predate mammals.[rx] The process of feeding milk in all animals (including humans) is called nursing, and in humans, it is also called breastfeeding. Newborn infants often produce some milk from their own breast tissue, known colloquially as witch’s milk.

In most species, lactation is a sign that the individual has been pregnant at some point in her life, with the exception of humans and goats.[rx][rx] Nearly every species of mammal has nipples; except for monotremes, egg-laying mammals, which instead release milk through ducts in the abdomen. In only one species of mammal, the Dayak fruit bat from Southeast Asia is milk production a normal male function.

Pathophysiology

Lactogenesis is the process of developing the ability to secrete milk and involves the maturation of alveolar cells. It takes place in 2 stages: secretory initiation and secretory activation.

Stage I lactogenesis (secretory initiation) takes place during the second half of pregnancy. The placenta supplies high levels of progesterone which inhibit further differentiation. In this stage, small amounts of milk can be secreted by week 16 gestation. By late pregnancy, some women can express colostrum.
Stage II lactogenesis (secretory activation) starts with copious milk production after delivery. With the removal of the placenta at delivery, the rapid drop in progesterone, as well as the presence of elevated levels of prolactin, cortisol, and insulin, are what stimulate this stage. Usually, at days 2 or 3 postpartum, most women experience swelling of the breast along with copious milk production. In primiparous women, the secretory activation stage is slightly delayed, and early milk volume is lower. Lower milk volume is also observed in women who had cesarean births compared with those who delivered vaginally. Late-onset of milk production has also been seen in women who have had retained placental fragments, diabetes, and stressful vaginal deliveries. With retained placental fragments, lactogenesis stage II could be inhibited by the continued secretion of progesterone and would continue to be inhibited until removal of the remaining placental fragments.

Lactation is maintained by regular removal of milk and stimulation of the nipple, which triggers prolactin release from the anterior pituitary gland and oxytocin from the posterior pituitary gland. For the ongoing synthesis and secretion of milk, the mammary gland must receive hormonal signals; and although prolactin and oxytocin act independently on different cellular receptors, their combined action is essential for successful lactation.

Prolactin is a polypeptide hormone synthesized by lactotrophic cells in the anterior pituitary and is structurally similar to growth hormone and placental lactogen. Prolactin is both positively and negatively regulated, but its main control comes from hypothalamic inhibitory factors such as dopamine which act on the D2 subclass of dopamine receptors present in lactotrophs. Prolactin stimulates mammary gland ductal growth and epithelial cell proliferation and induces milk protein synthesis. Emptying of the breast by the infant’s suckling is thought to be the most important factor. Prolactin concentration increases rapidly with suckling of the nipple which stimulates nerve endings located there.

Oxytocin is involved in the milk ejection or letdown reflex. The tactile stimulation of the nipple-areolar complex by suckling leads to afferent signals to the hypothalamus that trigger release of oxytocin. This results in the contraction of the myoepithelial cells, forcing milk into the ducts from the alveolar lumens and out through the nipple. Oxytocin also has a psychological effect, which includes inducing a state of calm, and reducing stress. It may also enhance feelings of affection between mother and child, an important factor in bonding.

Once lactation is established and maintained, production is regulated by the interaction of both physical and biochemical factors. If milk is not removed, elevated intramammary pressure and accumulation of a feedback inhibitor of lactation reduce milk production and initiate mammary involution. If breast milk is removed, the inhibitor is also removed, and secretion will resume. The role of the feedback inhibitor of lactation is to regulate the amount of milk produced which is determined by how much the baby takes, and therefore by how much the baby needs.

Physiology of Lactation

Lactation is the secretion of milk from specialized glands (mammary glands) to provide nourishment to offspring. Lactation is a hallmark feature of female mammals. Lactation is under endocrine control. The two main hormones involved are prolactin and oxytocin.

Lactogenesis, or the process of changes to the mammary glands to begin producing milk, begins during the late stages of pregnancy. The delivery of the placenta and the resulting dramatic reduction in progesterone, estrogen, and human placental lactogen levels stimulate milk production.

Colostrum is the first milk a breastfed baby receives. It contains higher amounts of white blood cells and antibodies than mature milk and is especially high in immunoglobulin A. This immunoglobulin coats the lining of the baby’s immature intestines, helping to prevent pathogens from invading the baby’s system.

Key Terms
witch’s milk: Witch’s milk or neonatal milk is milk secreted from the breasts of some newborn human infants of either sex. Neonatal milk secretion is considered a normal physiological occurrence and no treatment or testing is necessary.
mammary gland: A gland that secretes milk for suckling an infant or offspring.
lactation: 1. The secretion of milk from the mammary gland of a female mammal. 2. The process of providing the milk to the young, such as breastfeeding. 3. The period of time that a mother lactates to feed her young; the lactation period.
human placental lactogen: A hormone closely associated with prolactin that is
instrumental in breast, nipple, and areola growth before birth.
colostrum: A form of milk produced by the mammary glands in late pregnancy and the few days after giving birth. Human and bovine colostrum is thick and yellowish. In humans, it has high concentrations of nutrients and antibodies, but it is small in quantity.

Overview of Lactation

Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, although it predates the origin of mammals.

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In humans the process of feeding milk is called breastfeeding or nursing.
The chief function of lactation is to provide nutrition and immune protection to the young after birth. In almost all mammals, lactation induces a period of infertility, which serves to provide the optimal birth spacing for the survival of the offspring.

In most species, milk comes out of the mother’s nipples; however, the platypus (a non-placental mammal) releases milk through ducts in its abdomen. In only one species of mammal, the Dayak fruit bat is milk production a normal male function.

In some other mammals, the male may produce milk as the result of a hormone imbalance. This phenomenon may also be observed in newborn infants as well (for instance, witch’s milk).

Galactopoiesis is the maintenance of milk production. This stage requires prolactin and oxytocin.

Preparation for Lactation

By the fifth or sixth month of pregnancy, the breasts are ready to produce milk. During the latter part of pregnancy, the woman’s breasts enter into the lactogenesis I stage. This is when the breasts make colostrum, a thick, sometimes yellowish fluid.

At this stage, high levels of progesterone inhibit most milk production. It is not a medical concern if a pregnant woman leaks any colostrum before her baby’s birth, nor is it an indication of future milk production.

At birth, prolactin levels remain high, while the delivery of the placenta results in a sudden drop in progesterone, estrogen, and human placental lactogen levels. This abrupt withdrawal of progesterone in the presence of high prolactin levels stimulates the copious milk production of the lactogenesis II stage.

When the breast is stimulated, prolactin levels in the blood rise and peak in about 45 minutes, then return to the pre-breastfeeding state about three hours later. The release of prolactin triggers the cells in the alveoli to make milk.

Colostrum

Colostrum is the first milk a breastfed baby receives. It contains higher amounts of white blood cells and antibodies than mature milk, and is especially high in immunoglobulin A (IgA), which coats the lining of the baby’s immature intestines, and helps to prevent pathogens from invading the baby’s system. Secretory IgA also helps prevent food allergies. Over the first two weeks after the birth, colostrum production slowly gives way to mature breast milk.

Lactation: A positive feedback loop ensures continued milk production as long as the infant continues to breastfeed.

Hormonal influences

From the eighteenth week of pregnancy (the second and third trimesters), a woman’s body produces hormones that stimulate the growth of the milk duct system in the breasts:

Progesterone influences the growth in the size of alveoli and lobes; high levels of progesterone inhibit lactation before birth. Progesterone levels drop after birth; this triggers the onset of copious milk production.[
Estrogen stimulates the milk duct system to grow and differentiate. Like progesterone, high levels of estrogen also inhibit lactation. Estrogen levels also drop at delivery and remain low for the first several months of breastfeeding.[rx] Breastfeeding mothers should avoid estrogen-based birth control methods, as a spike in estrogen levels may reduce a mother’s milk supply.
Prolactin contributes to the increased growth and differentiation of the alveoli and also influences the differentiation of ductal structures. High levels of prolactin during pregnancy and breastfeeding also increase insulin resistance, increase growth factor levels (IGF-1) and modify lipid metabolism in preparation for breastfeeding. During lactation, prolactin is the main factor maintaining tight junctions of the ductal epithelium and regulating milk production through osmotic balance.
Human placental lactogen (HPL) – from the second month of pregnancy, the placenta releases large amounts of HPL. This hormone is closely associated with prolactin and appears to be instrumental in breast, nipple, and areola growth before birth.
Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG), through control of estrogen and progesterone production, and also, by extension, prolactin and growth hormone production, are essential.
Growth hormone (GH) is structurally very similar to prolactin and independently contributes to its galactopoiesis.
Adrenocorticotropic hormone (ACTH) and glucocorticoids such as cortisol have an important lactation-inducing function in several animal species, including humans. Glucocorticoids play a complex regulating role in the maintenance of tight junctions.
Thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) are very important galactopoietic hormones whose levels are naturally increased during pregnancy.
Oxytocin contracts the smooth muscle of the uterus during and after birth, and during orgasm(s). After birth, oxytocin contracts the smooth muscle layer of band-like cells surrounding the alveoli to squeeze the newly produced milk into the duct system. Oxytocin is necessary for the milk ejection reflex, or let-down, in response to suckling, to occur.

It is also possible to induce lactation without pregnancy. Protocols for inducing lactation are called the Goldfarb protocols. Using birth control pills to mimic the hormone levels of pregnancy, then discontinuing the birth control, followed by use of a double electric breast pump for 15 minute sessions at regular 2-3 hour intervals (100+ minutes total per day) helps to induce milk production.

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Secretory differentiation

During the latter part of pregnancy, the woman’s breasts enter into the Secretory Differentiation stage. This is when the breasts make colostrum (see below), a thick, sometimes yellowish fluid. At this stage, high levels of progesterone inhibit most milk production. It is not a medical concern if a pregnant woman leaks any colostrum before her baby’s birth, nor is it an indication of future milk production.

Secretory activation

At birth, prolactin levels remain high, while the delivery of the placenta results in a sudden drop in progesterone, estrogen, and HPL levels. This abrupt withdrawal of progesterone in the presence of high prolactin levels stimulates the copious milk production of Secretory Activation.

When the breast is stimulated, prolactin levels in the blood rise, peak in about 45 minutes, and return to the pre-breast feeding state about three hours later. The release of prolactin triggers the cells in the alveoli to make milk. Prolactin also transfers to breast milk. Some research indicates that prolactin in milk is greater at times of higher milk production, and lower when breasts are fuller and that the highest levels tend to occur between 2 a.m. and 6 a.m.[rx]

Other hormones—notably insulin, thyroxine, and cortisol—are also involved, but their roles are not yet well understood. Although biochemical markers indicate that Secretory Activation begins about 30–40 hours after birth, mothers do not typically begin feeling increased breast fullness (the sensation of milk “coming in the breast”) until 50–73 hours (2–3 days) after birth.

Colostrum is the first milk a breastfed baby receives. It contains higher amounts of white blood cells and antibodies than mature milk, and is especially high in immunoglobulin A (IgA), which coats the lining of the baby’s immature intestines, and helps to prevent pathogens from invading the baby’s system. Secretory IgA also helps prevent food allergies.[rx] Over the first two weeks after the birth, colostrum production slowly gives way to mature breast milk.[rx]

Autocrine control – Galactopoiesis

The hormonal endocrine control system drives milk production during pregnancy and the first few days after birth. When the milk supply is more firmly established, the autocrine (or local) control system begins.

During this stage, the more that milk is removed from the breasts, the more the breast will produce milk.[rx][rx] Research also suggests that draining the breasts more fully also increases the rate of milk production.[11] Thus the milk supply is strongly influenced by how often the baby feeds and how well it is able to transfer milk from the breast. Low supply can often be traced to:

  • not feeding or pumping often enough
  • inability of the infant to transfer milk effectively caused by, among other things:
  • jaw or mouth structure deficits
  • poor latching technique
  • rare maternal endocrine disorders
  • hypoplastic breast tissue
  • inadequate calorie intake or malnutrition of the mother

Milk ejection reflex

This is the mechanism by which milk is transported from the breast alveoli to the nipple. Suckling by the baby stimulates the paraventricular nuclei and supraoptic nucleus in the hypothalamus, which signals to the posterior pituitary gland to produce oxytocin. Oxytocin stimulates the contraction of the myoepithelial cells surrounding the alveoli, which already hold milk. The increased pressure causes milk to flow through the duct system and be released through the nipple. This response can be conditioned e.g. to the cry of the baby.

Milk ejection is initiated in the mother’s breast by the act of suckling by the baby. The milk ejection reflex (also called the let-down reflex) is not always consistent, especially at first. Once a woman is conditioned to nursing, let-down can be triggered by a variety of stimuli, including the sound of any baby. Even thinking about breastfeeding can stimulate this reflex, causing unwanted leakage, or both breasts may give out milk when an infant is feeding on one breast. However, this and other problems often settle after two weeks of feeding. Stress or anxiety can cause difficulties with breastfeeding. The release of the hormone oxytocin leads to the milk ejection or let-down reflex. Oxytocin stimulates the muscles surrounding the breast to squeeze out the milk. Breastfeeding mothers describe the sensation differently. Some feel a slight tingling, others feel immense amounts of pressure or slight pain/discomfort, and still, others do not feel anything different.

A poor milk ejection reflex can be due to sore or cracked nipples, separation from the infant, a history of breast surgery, or tissue damage from prior breast trauma. If a mother has trouble breastfeeding, different methods of assisting the milk ejection reflex may help. These include feeding in a familiar and comfortable location, massage of the breast or back, or warming the breast with a cloth or shower.

Milk ejection reflex mechanism

This is the mechanism by which milk is transported from the breast alveoli to the nipple. Suckling by the baby innervates slowly-adapting[rx] and rapidly adapting [rx] mechanoreceptors that are densely packed around the areolar region. The electrical impulse follows the spinothalamic tract, which begins by innervation of the fourth intercostal nerve. The electrical impulse then ascends the posterolateral tract for one or two vertebral levels and synapses with second-order neurons, called tract cells, in the posterior dorsal horn. The tract cells then decussate via the anterior white commissure to the anterolateral corner and ascend to the supraoptic nucleus and paraventricular nucleus in the hypothalamus, where they synapse with oxytocinergic third-order neurons. The somas of these neurons are located in the hypothalamus, but their axon and axon terminals are located in the infundibulum and pars nervosa of the posterior pituitary, respectively. The oxytocin is produced in the neuron’s soma in the supraoptic and paraventricular nuclei and is then transported down the infundibulum via the hypothalamic-neurohypophyseal tract with the help of the carrier protein, neurophysin I, to the pars nervosa of the posterior pituitary, and then stored in Herring bodies, where they are stored until the synapse between second-and third-order neurons.

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Following the electrical impulse, oxytocin is released into the bloodstream. Through the bloodstream, oxytocin makes its way to myoepithelial cells, which lie between the extracellular matrix and luminal epithelial cells that also make up the alveoli in breast tissue. When oxytocin binds to the myoepithelial cells, the cells contract. The increased intra-alveolar pressure forces milk into the lactiferous sinuses, into the lactiferous ducts (a study found that lactiferous sinuses may not exist.[rx] If this is true then milk simply enters the lactiferous ducts), and then out the nipple.

Afterpains

A surge of oxytocin also causes the uterus to contract. During breastfeeding, mothers may feel these contractions as afterpains. These may range from period-like cramps to strong labor-like contractions and can be more severe with second and subsequent babies. [rx][rx]

Without pregnancy, induced lactation, relaxation

In humans, induced lactation and relaxation have been observed frequently in some cultures, and demonstrated with varying success in adoptive mothers. It appears plausible that the possibility of lactation in women (or females of other species) who are not biological mothers does confer an evolutionary advantage, especially in groups with high maternal mortality and tight social bonds.[rx][rx] The phenomenon has been also observed in most primates, in some lemurs, and in dwarf mongooses.[rx][rx]

Lactation can be induced in humans by a combination of physical and psychological stimulation, by drugs, or by a combination of those methods.[rx] Some couples may stimulate lactation outside of pregnancy for sexual purposes.

Rare accounts of male lactation (as distinct from galactorrhea) exist in historical medical and anthropological literature, although the phenomenon has not been confirmed by more recent literature.[rx]

Domperidone is a drug that can induce lactation.[rx][rx]

Development

During puberty, lobule type 1 is formed. Changes in the level of estrogen and progesterone during each menstrual cycle stimulate lobule 1 to produce new alveolar buds and eventually evolve to more mature structures, known as type-2 and type-3 lobules. Once puberty is complete, no further changes occur to the female breast until pregnancy.

During pregnancy, stage-II mammogenesis (alveolar development and maturation of the epithelium) occurs largely in response to higher levels of progesterone. The increased volume of breast tissue during pregnancy is a result of the proliferation of secretory tissue. In early pregnancy, lobule type 3 is formed due to the influence of chorionic gonadotropin. These newly formed lobules have larger size and number of epithelial cells composing each acinus. In late pregnancy, the proliferation of new acini is reduced, and the lumen becomes distended with secretory material or colostrum.

During labor and lactation, further growth and differentiation can be seen in the lobule along with milk secretion. The glandular component of the breast has now increased to the point where it is mainly formed of epithelial elements and very little stroma. This will persist throughout lactation.

Finally, the involution of mammary glands occurs with the cessation of lactation and requires a combination of lactogenic hormone deprivation and local autocrine signals that signal apoptotic cell death and tissue remodeling. Full regression does not occur, and pregnancy causes a permanent increase in the size and number of lobules. Following lactation, there is always the potential of the glands to produce milk in response to regular stimulation.

Organ Systems Involved

Normal lactation involves the female breast, anterior lobe of the pituitary, and posterior lobe of the pituitary. Their roles in lactation are discussed below.

Function

The decision to breastfeed or to provide breast milk via expression is a decision that every mother must make. Clinicians must inform our patients about all the benefits that breast milk can provide to their newborns. Breast milk provides ideal nutrition for infants with vitamins, proteins, and fats that are more easily digested than formula. Breast milk contains antibodies from the mother that help babies fight off viruses and bacteria. Other anti-infective factors it provides include immunoglobulin (IgA in particular), white blood cells, whey protein (lysozyme and lactoferrin), and oligosaccharides. It also lowers the baby’s risk of asthma, allergies, ear infections, respiratory illnesses, bouts of diarrhea, and the risk of diabetes and obesity.

References

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