Physiology of Lactation

1. Development of the Breast (Mammogenesis)

• Estrogens (from puberty onward) stimulate growth of the ductal system and fat deposition. During pregnancy, placental estrogens cause the ductal system to grow and branch extensively.
• Progesterone (during pregnancy) drives full development of the lobule-alveolar system - it stimulates budding of alveoli and secretory differentiation of alveolar cells.
• Supporting hormones include: growth hormone, prolactin, adrenal glucocorticoids, and insulin - all involved in protein metabolism needed for breast tissue growth.

2. Initiation of Lactation (Lactogenesis) - Role of Prolactin

• During pregnancy, prolactin levels rise steadily from the 5th week to 10-20 times the normal level by term.
• Why doesn't lactation occur during pregnancy? Despite high prolactin levels, high estrogen and progesterone from the placenta block prolactin's action on the breast - suppressing actual milk secretion.
• At parturition, the sudden fall in estrogen and progesterone (after placental delivery) removes this inhibition, and prolactin can now act freely - milk secretion begins within 1-7 days.
• The fluid secreted in the first few days before and after birth is colostrum - rich in proteins, immunoglobulins, and lactose, but low in fat.

3. Maintenance of Lactation - Suckling Reflex

• Suckling sends afferent nerve impulses from nipple mechanoreceptors → hypothalamus → causes a 10-20-fold surge in prolactin lasting ~1 hour.
• This surge keeps alveolar cells secreting milk for the next nursing period.
• Without regular suckling, milk production ceases within ~1 week.

• Suckling (and also auditory, visual, olfactory stimuli associated with the baby) → hypothalamic nuclei → posterior pituitary releases oxytocin.
• Oxytocin causes contraction of myoepithelial cells surrounding the alveoli and ducts → milk is ejected through the nipple (let-down reflex).
• Emotional stress can inhibit oxytocin release and thus inhibit milk let-down.

4. Hypothalamic Control of Prolactin

• Prolactin Inhibitory Hormone (PIH) = Dopamine, secreted by arcuate nucleus, travels via portal system to anterior pituitary, suppressing prolactin up to 10-fold.
• Suckling suppresses dopamine release → allows prolactin surge.
• Drugs blocking dopamine (e.g., antipsychotics) can cause galactorrhea; dopamine agonists (e.g., bromocriptine) suppress lactation.
• Prolactin Releasing Factor (PRF): TRH also has a minor prolactin-releasing effect.

5. Lactation Amenorrhea

• Elevated prolactin → inhibits GnRH secretion from hypothalamus → suppresses FSH and LH from anterior pituitary → ovulation is suppressed.
• This is the basis of lactational amenorrhea - breast-feeding acts as a natural (though not 100% effective) contraceptive method.

Summary Table

Physiology of Lactation

1. Development of the Breast (Mammogenesis)

• Estrogens stimulate growth of the ductal system and fat deposition. During pregnancy, placental estrogens cause the ductal system to grow and branch extensively.
• Progesterone drives full development of the lobule-alveolar system - stimulates budding of alveoli and secretory differentiation of alveolar cells.
• Supporting hormones: growth hormone, prolactin, adrenal glucocorticoids, and insulin - all involved in protein metabolism needed for breast tissue growth.

2. Initiation of Lactation (Lactogenesis) - Role of Prolactin

• During pregnancy, prolactin levels rise steadily from the 5th week to 10-20 times the normal level by term.
• Why doesn't lactation occur during pregnancy? Despite high prolactin, high estrogen and progesterone from the placenta block prolactin's action on the breast - suppressing actual milk secretion.
• At parturition, the sudden fall in estrogen and progesterone (after placental delivery) removes this inhibition - milk secretion begins within 1-7 days.
• The fluid secreted in the first few days is colostrum - rich in proteins and immunoglobulins, low in fat.

3. Maintenance of Lactation - Suckling Reflex

• Suckling → afferent nerve impulses from nipple mechanoreceptors → hypothalamus → 10-20-fold surge in prolactin lasting ~1 hour.
• This surge keeps alveolar cells secreting milk for the next nursing period.
• Without regular suckling, milk production ceases within ~1 week.

• Suckling (and also auditory, visual, olfactory stimuli associated with the baby) → hypothalamic nuclei → posterior pituitary releases oxytocin.
• Oxytocin causes contraction of myoepithelial cells surrounding the alveoli and ducts → milk is ejected through the nipple.
• Emotional stress can inhibit oxytocin release and thus inhibit milk let-down.

4. Hypothalamic Control of Prolactin

• Prolactin Inhibitory Hormone (PIH) = Dopamine, secreted by the arcuate nucleus, travels via the hypothalamo-hypophysial portal system to suppress prolactin secretion up to 10-fold.
• Suckling suppresses dopamine release → allows the prolactin surge.
• Drugs blocking dopamine (e.g., antipsychotics) can cause galactorrhea; dopamine agonists (e.g., bromocriptine) suppress lactation.
• TRH has a minor prolactin-releasing effect.

5. Lactation Amenorrhea

• Elevated prolactin → inhibits GnRH secretion from hypothalamus → suppresses FSH and LH from anterior pituitary → ovulation is suppressed.
• This is the basis of lactational amenorrhea - breast-feeding acts as a natural (though not 100% effective) contraceptive.

Summary Table

Section IV – Explain the Physiological Basis (4 Marks Each)

1. Puberty

• The primary event at puberty is the initiation of pulsatile GnRH secretion from the hypothalamus (previously suppressed by a CNS inhibitory mechanism in childhood).
• Pulsatile GnRH → pulsatile FSH and LH release from anterior pituitary.
• Males: LH → Leydig cells → testosterone → secondary sexual characters (beard, voice change, muscle growth). FSH + testosterone → spermatogenesis.
• Females: FSH → follicular development → estrogen → breast development, uterine growth, menarche. LH surge → ovulation.
• Adrenarche: Adrenal androgens (DHEA) cause pubic and axillary hair in both sexes.
• Early puberty shows nocturnal LH pulses (sleep-entrained gonadotropin surges).

2. Sertoli Cells are Important in Spermatogenesis

3. Sterility in Undescended Testis / Spermatogenesis Markedly Reduced

• Normally the testes descend into the scrotum where the temperature is 2-3°C lower than core body temperature (scrotal temp ~34°C vs. body temp 37°C).
• Spermatogenesis requires this lower temperature - the enzymes involved in meiosis and spermiogenesis are heat-sensitive.
• In cryptorchidism, the testis remains in the inguinal canal or abdomen at 37°C.
• This higher temperature damages the germinal epithelium (spermatogonia degenerate) → markedly reduced or absent spermatogenesis → sterility.
• Leydig cells are more heat-resistant - so testosterone secretion and secondary sexual characters are usually preserved.
• The scrotum maintains low temperature via the pampiniform plexus (countercurrent heat exchange) and cremaster muscle reflexes.

4. Sterility in Man Working in Hot Surroundings

• Same fundamental principle: spermatogenesis requires scrotal temperature 2-3°C below core body temperature.
• Men working continuously in hot environments (furnace workers, bakers, welders) have persistently elevated scrotal temperatures.
• Even a rise of 1-2°C above normal scrotal temperature impairs spermatogenesis.
• Prolonged heat exposure → degeneration of germinal epithelium → oligospermia or azoospermia → infertility.
• The normal thermoregulatory mechanisms (pampiniform plexus, cremaster muscle) are overwhelmed by sustained environmental heat.
• This is potentially reversible if heat exposure is removed and the germinal epithelium recovers.
• Same principle explains why tight underwear, hot baths, and laptop use on the lap can reduce sperm counts.

5. Anemia in Hypogonadism of Male

• Testosterone has a direct stimulatory effect on erythropoiesis (RBC production) through two mechanisms:
  1. Stimulates the kidneys to secrete erythropoietin (EPO) → EPO acts on bone marrow → increases RBC production.
  2. Direct stimulation of bone marrow erythroid stem cells.
• In hypogonadism (testicular failure or hypopituitarism), testosterone levels are very low.
• Low testosterone → decreased EPO → decreased RBC production → normocytic normochromic anemia.
• This explains why normal males have higher hemoglobin (15.5 g/dL) than females (14 g/dL) - due to testosterone.
• Testosterone replacement therapy in hypogonadal males corrects the anemia.

6. Body Temperature is Slightly Elevated After Ovulation

• After ovulation, the ruptured Graafian follicle becomes the corpus luteum, which secretes large amounts of progesterone.
• Progesterone has a thermogenic (heat-producing) effect - acts on the hypothalamic thermoregulatory center to raise the temperature set-point.
• Basal body temperature (BBT) rises by 0.2-0.5°C (about 0.5°F) after ovulation and remains elevated throughout the luteal phase (~14 days).
• When corpus luteum regresses before menstruation → progesterone falls → BBT drops back to baseline.
• Clinical use: BBT charting confirms ovulation has occurred (biphasic chart = ovulatory cycle). However, since the rise occurs 1-2 days after ovulation, it predicts the next cycle rather than the current one.

7. Menstrual Blood Does Not Clot

1. Fibrinolysin (Plasmin): The shedding endometrium produces large amounts of fibrinolysin - this enzyme breaks down fibrin clots as quickly as they form, preventing coagulation.
2. Prostaglandins (PGE2, PGF2α): Present in high amounts in menstrual blood; promote fibrinolysis.
3. Tissue thromboplastin released is minimal compared to the overwhelming fibrinolytic activity.
4. Menstrual bleeding is from small spiral arterioles - the flow dynamics differ from wound bleeding.

• If flow is excessively heavy (menorrhagia), fibrinolysin is insufficient to lyse all clots → clots appear in heavy flow, which is considered abnormal.

8. Immunological Test of Pregnancy

• After implantation (~day 8-10), the trophoblast cells secrete human Chorionic Gonadotropin (hCG) into maternal blood and urine.
• hCG is a glycoprotein with antigenic properties and a unique β subunit (β-hCG).
• Animals (rabbits/sheep) immunized with hCG produce anti-hCG antibodies.

• Patient's urine + anti-hCG antibodies + hCG-coated particles:
  • Pregnant (hCG present in urine): hCG neutralizes antibodies → agglutination inhibited = Positive.
  • Not pregnant (no hCG): Antibodies react with particles → agglutination occurs = Negative.
• Modern home pregnancy tests use monoclonal anti-β-hCG antibodies on a lateral flow strip.
• Also positive in: hydatidiform mole, choriocarcinoma, ectopic pregnancy (all produce hCG).

9. Ectopic Pregnancy

• Fertilization normally occurs in the ampulla of the fallopian tube. The embryo is transported to the uterus by:
  • Ciliary beating of tubal epithelium
  • Peristaltic muscular contractions of the tube
  • Tubal fluid current
• If transport is impaired, the embryo implants in the tube.

• Salpingitis/PID - scarring destroys cilia and impairs muscular contractions
• Previous tubal surgery, endometriosis, congenital tubal abnormality

• The fallopian tube cannot expand like the uterus to accommodate the growing embryo.
• The trophoblast erodes through the thin tubal wall → tube ruptures at 6-8 weeks → life-threatening intraperitoneal hemorrhage.

10. Corticosteroids are Administered to a Lady in Preterm Labour

• The major risk of premature birth (before 34 weeks) is Respiratory Distress Syndrome (RDS) / Hyaline Membrane Disease in the newborn.
• RDS occurs because fetal lungs are immature - insufficient pulmonary surfactant.
• Surfactant (dipalmitoyl phosphatidylcholine) is produced by Type II pneumocytes. It reduces alveolar surface tension and prevents alveolar collapse at end-expiration.
• Surfactant production is triggered by cortisol - fetal cortisol normally rises in the last weeks of pregnancy (34-36 weeks) to mature the lungs naturally.
• In preterm labour, this cortisol surge has not yet occurred.

• Betamethasone or Dexamethasone (given to mother) → cross the placenta → act on fetal Type II pneumocytes → accelerate surfactant synthesis within 24-48 hours → lung maturity is achieved.
• Significantly reduces RDS, neonatal mortality, and intraventricular hemorrhage.

11. Safe Period as a Contraceptive Method

• Conception requires a viable sperm to meet a viable ovum.
• Ovum viability: Ovum survives only 12-24 hours after ovulation.
• Sperm viability: Sperms survive in the female tract for 48-72 hours (up to 5 days).
• Therefore, pregnancy is only possible during a narrow fertile window around ovulation.

• Ovulation on Day 14 (±2 days).
• Unsafe (fertile) period = Day 10 to Day 17.
• Safe period = Day 1-9 (post-menstrual) and Day 18-28 (pre-menstrual).

• Unreliable in women with irregular cycles.
• Relatively high failure rate (~20%).
• Also called the rhythm method / calendar method.

12. Contraceptive Pills

• Pills create an artificial luteal-phase environment - the pituitary "thinks" the woman is already pregnant (high estrogen + progesterone) → suppresses gonadotropins.
• Taken for 21 days, 7-day pill-free interval → withdrawal bleed occurs.
• Failure rate: <1% with perfect use.

13. Intra-Uterine Contraceptive Devices (IUCDs) Prevent Pregnancy

1. Foreign body reaction: IUCD causes a sterile inflammatory reaction in the endometrium → increased leucocytes, macrophages, and prostaglandins → hostile environment for sperms (phagocytosed) and implantation.
2. Altered uterine and tubal motility: Prostaglandins impair sperm transport and ovum pick-up.
3. Endometrial changes: Inflammatory reaction makes endometrium biochemically unsuitable for implantation of the blastocyst.
4. Hormone-releasing IUDs (Mirena): Additionally thicken cervical mucus and suppress endometrium.

• IUCDs generally do not prevent ovulation (except hormonal IUDs partially).
• Failure rate: ~0.5-1% per year - highly effective.

14. Copper-T

1. Spermicidal action of copper ions (Cu²⁺):
   • Cu²⁺ ions released continuously into uterine cavity.
   • Directly toxic to sperms - impairs sperm motility, inhibits acrosomal enzyme activity, alters sperm membrane → sperms cannot fertilize the ovum.
2. Enhanced inflammatory reaction - copper intensifies leucocytic response in endometrium.
3. Endometrial biochemical changes - copper ions further impair implantation.
4. Cervical mucus changes - copper ions make mucus more hostile to sperms.

• More effective than plain IUCDs due to added spermicidal effect.
• Effective for 5-10 years.
• Can be used as emergency contraception if inserted within 5 days of unprotected intercourse.
• Failure rate: 0.6-0.8% per year.

Sources: Guyton & Hall Textbook of Medical Physiology | Ganong's Review of Medical Physiology (26th ed.) | Costanzo Physiology (7th ed.) | Robbins & Kumar Basic Pathology