Physiology of Pregnancy and Birth - Guyton & Hall

1. Maturation and Fertilization of the Ovum

2. Implantation of the Blastocyst

3. Anatomy and Function of the Placenta

• Fetal blood flows via two umbilical arteries → villus capillaries → single umbilical vein back to fetus
• Maternal blood flows from uterine arteries → large maternal sinuses surrounding the villi → uterine veins

• Oxygen by diffusion (fetal hemoglobin has higher O2 affinity than maternal hemoglobin)
• Glucose, amino acids, fatty acids to the fetus
• CO2 and urea from fetus to mother
• IgG antibodies (passive immunity to the neonate)
• Various drugs, alcohol, nicotine, and some viruses can cross the membrane

4. Hormonal Factors in Pregnancy

Human Chorionic Gonadotropin (hCG)

• Secreted by syncytial trophoblast cells; detectable in blood 8-9 days after ovulation
• Peaks at 10-12 weeks, then falls to a lower plateau for the rest of pregnancy
• Key function: Prevents involution of the corpus luteum - instead, the corpus luteum grows to ~twice its size and continues secreting progesterone and estrogens, preventing menstruation and maintaining the decidua
• If the corpus luteum is removed before week 7, abortion almost always results; removal between weeks 7-12 risks abortion; after week 12-13, the placenta itself secretes enough progesterone/estrogen
• Also stimulates the fetal testes to produce testosterone (required for male genital development)
• Forms the basis of pregnancy tests (urine/serum hCG)

Estrogens

• Secreted by the placenta, primarily as estriol (unlike ovarian estradiol)
• Require androgenic precursors from both the fetal and maternal adrenal cortices (placenta lacks full steroid synthesis machinery)
• Effects in pregnancy:
  • Enlargement of uterus, breasts, and external genitalia
  • Breast ductal growth
  • Relaxation of pelvic ligaments (pelvis widens for delivery)
  • Increased uterine contractility (especially near term)
  • Fluid retention

Progesterone

• Secreted in increasing amounts throughout pregnancy
• Inhibits uterine contractility - essential for keeping the fetus in utero
• Promotes decidual cell development for early fetal nutrition
• Prepares the breasts for lactation (alveolar development)
• Suppresses the maternal immune rejection of the fetus

Human Chorionic Somatomammotropin (hCS / hPL)

• Secreted progressively throughout pregnancy; at term, ~1 gram/day (largest hormone output of any endocrine gland)
• Structurally similar to growth hormone
• Decreases maternal insulin sensitivity - causes mild diabetic-like state, sparing glucose for the fetus
• Promotes lipolysis in the mother, providing fatty acids as maternal fuel
• Mild anabolic and lactogenic effects

Other Hormones

• Relaxin (from corpus luteum, then placenta) - relaxes the pubic symphysis and cervical ligaments
• Increased cortisol, aldosterone, thyroxine during pregnancy
• Prolactin rises progressively

5. Response of the Mother's Body to Pregnancy

Body Changes

• Uterus: 50 g → ~1100 g
• Breasts approximately double in size
• Average weight gain: 25-35 lbs - ~8 lb fetus, 4 lb placenta/membranes/fluid, 3 lb uterus, 2 lb breasts, 5 lb extra blood/ECF, 3-13 lb fat stores

Metabolism

• Basal metabolic rate increases ~15% in the latter half of pregnancy due to elevated thyroxine, adrenocortical hormones, sex hormones, and added fetal tissue

Nutrition

• The fetus almost doubles in weight in the last 2 months
• Key needs: protein, calcium, phosphate, iron (fetus needs ~375 mg iron for blood; mother needs ~600 mg extra for her own)
• Hypochromic anemia is common if iron intake is inadequate
• Vitamin D is critical for calcium absorption
• Vitamin K is given near term to prevent neonatal hemorrhage

Circulatory Changes

• Cardiac output increases 30-40% above normal by the third trimester
• Blood volume increases ~30% (extra plasma + red cells)

Respiratory Changes

• Tidal volume and minute ventilation increase significantly (partly due to progesterone acting as a respiratory stimulant)
• Slight respiratory alkalosis is normal

Kidney Function

• Glomerular filtration rate (GFR) increases ~50%
• Renal plasma flow increases
• Glucosuria can occur even with normal blood glucose (due to increased filtered load exceeding tubular reabsorption capacity)
• Aldosterone rises, promoting Na+ retention; but progesterone competes with aldosterone at the tubule

6. Parturition - Birth of the Baby

Hormonal Factors Increasing Uterine Contractility

1. Estrogen/Progesterone ratio shift: From the 7th month onward, estrogen secretion continues rising while progesterone stays flat or slightly decreases. The rising estrogen-to-progesterone ratio increases uterine excitability - estrogen increases gap junctions between uterine smooth muscle cells, synchronizing contractions.
2. Oxytocin: The uterus increases its oxytocin receptors near term, greatly amplifying its response. Oxytocin secretion from the neurohypophysis increases during labor. Cervical irritation/stretching triggers a neuroendocrine reflex through the hypothalamus to increase oxytocin release (Ferguson reflex).
3. Fetal hormones: The fetal pituitary secretes oxytocin; fetal adrenals secrete cortisol; fetal membranes release prostaglandins in high concentrations - all contributing to uterine stimulation.

Mechanical Factors

• Stretch of uterine musculature (smooth muscle contractility increases with stretch) - explains why twins are born ~19 days earlier on average
• Cervical stretch/irritation triggers oxytocin release via the hypothalamus

Positive Feedback Mechanism of Labor (Ferguson Reflex)

1. Uterine contractions push the fetal head against the cervix
2. Cervical stretching sends nerve signals to the hypothalamus
3. Hypothalamus triggers oxytocin release from the neurohypophysis
4. Oxytocin causes stronger uterine contractions
5. Stronger contractions push the head harder against the cervix
6. This continues until the baby is delivered and the cycle breaks

Stages of Labor

• First Stage: Progressive cervical dilation until the cervix is as wide as the fetal head. Lasts 8-24 hours in first delivery, may be only minutes in subsequent ones. Pain from uterine muscle hypoxia (visceral pain via hypogastric nerves).
• Second Stage: After full cervical dilation, fetal membranes rupture, amniotic fluid escapes, and the head descends through the birth canal. Lasts 1 minute to 30+ minutes. Pain is somatic (cervical, perineal, and vaginal stretching via somatic nerves) - much more intense.
• Third Stage (Placental delivery): Uterus contracts for 10-45 minutes post-delivery, shearing the placenta from the uterine wall. Average blood loss ~350 mL, limited by:
  • Figure-of-eight smooth muscle arrangement around uterine vessels - uterine contraction directly compresses the vessels
  • Vasoconstrictive prostaglandins at the separation site

7. Involution of the Uterus After Delivery and Lactation

• Placental hormones drop rapidly
• Uterus involutes back toward normal size over about 4-6 weeks
• Retained fluid (5 lbs extra) is excreted in the first few days postpartum as the fluid-retaining hormones (estrogen, progesterone, aldosterone) fall