Pregnancy physiology
Pregnancy physiology: placental hormones, maternal changes, labour and lactation
Placental hormones, maternal cardiovascular, respiratory, renal and metabolic changes, and the control of labour and lactation, for FCPS Part 1. Covers hCG, hPL and insulin resistance, aortocaval compression, Sheehan syndrome, tocolysis and breast milk.
One of the most tested topics in past papers
Placental hormones
| Hormone | Source | Roles |
|---|---|---|
| hCG | Syncytiotrophoblast | Rescues the corpus luteum until the placenta takes over at 8–10 weeks; peaks at 8–10 weeks then falls; TSH-like action (hyperemesis, gestational thyrotoxicosis); very high in molar and multiple pregnancy |
| Progesterone | Corpus luteum, then placenta | Maintains decidua, relaxes myometrium and other smooth muscle, stimulates breathing, raises temperature, develops breast alveoli |
| Oestrogens (mainly oestriol) | Placenta, from fetal adrenal DHEA-S converted in fetal liver | Uterine and breast duct growth, raise hepatic proteins (TBG, clotting factors); oestriol reflects fetoplacental wellbeing |
| Human placental lactogen (hPL) | Syncytiotrophoblast | Insulin resistance, maternal lipolysis, spares glucose for the fetus |
| Relaxin | Corpus luteum, placenta | Softens ligaments and cervix |
| CRH | Placenta | Rises towards term; helps time labour |
| Placental ALP | Placenta | Raises maternal ALP two- to fourfold in late pregnancy, with normal bilirubin, ALT and bile acids |
- hCG in early pregnancy: detectable in serum about 8–10 days after ovulation; serum β-hCG immunoassay is the most sensitive test before a missed period. In a normal early intrauterine pregnancy, hCG roughly doubles every 48 hours; a slower rise suggests ectopic or failing pregnancy.
- Luteoplacental shift: from about 8–10 weeks, oestrogen and progesterone come mainly from the placenta, so they are placental at 7 months and in the third trimester.
- FSH and LH do not rise in pregnancy; they are suppressed by high sex steroids. hCG falls in the second trimester while other placental hormones rise.
Maternal adaptations
| System | Change | Consequence |
|---|---|---|
| Cardiovascular | Plasma volume up about 40–50%, red cell mass up 20–30%; cardiac output up about 40%; systemic vascular resistance falls | Dilutional anaemia; BP lowest in second trimester |
| Supine position | Gravid uterus compresses the IVC and aorta (aortocaval compression) from about 20 weeks | Supine hypotension: pale, sweaty, faint; turn her onto her left side; manual uterine displacement in maternal CPR |
| Respiratory | Progesterone increases respiratory centre sensitivity to CO₂; tidal volume and minute ventilation up about 40%; PaCO₂ falls to about 4 kPa (30 mmHg); FRC falls | Compensated respiratory alkalosis; the sense of breathlessness is due to this hyperventilation |
| Renal | Renal plasma flow and GFR up about 50%; ureters dilate (progesterone, compression, right more than left) | Low urea and creatinine; glycosuria; urinary stasis and pyelonephritis; mild right hydronephrosis is normal |
| Haematological | Fibrinogen and factors VII, VIII, X up; protein S down | Hypercoagulable: venous thromboembolism risk |
| GI | Progesterone relaxes smooth muscle | Reflux, constipation, gallstones |
| Metabolic | hPL, cortisol and progesterone cause insulin resistance | Gestational diabetes; insulin needs rise and fall sharply once the placenta is delivered, risking postnatal hypoglycaemia |
| Thyroid | TBG up; hCG stimulates TSH receptor | Total T4 up, free T4 normal; first-trimester TSH lower |
| Nutrition | Extra energy about 350 kcal/day in later pregnancy; more iron and folate | Folic acid before conception and in early pregnancy prevents neural tube defects |
- Hyperemesis gravidarum (linked to high hCG) causes vomiting with hypochloraemic, hypokalaemic metabolic alkalosis and ketosis.
- In early pregnancy, subclinical hypothyroidism with positive TPO antibodies (TSH above the pregnancy range) is treated with levothyroxine.
- Gestational diabetes screening uses a 75 g OGTT at 24–28 weeks in women at risk.
- Pre-eclampsia: new hypertension after 20 weeks with proteinuria or organ dysfunction, from abnormal placentation and endothelial damage.
Labour (parturition)
- Quiescence (progesterone, relaxin, nitric oxide) gives way to activation: a rising oestrogen:progesterone ratio (functional progesterone withdrawal) increases oxytocin receptors, gap junctions (connexin 43) and prostaglandins. Fetal adrenal cortisol and placental CRH help time this; the placenta and fetal membranes are key organs.
- Cervical ripening: prostaglandins (PGE₂, dinoprostone) break down and remodel cervical collagen and increase water content; the cervix softens, shortens and dilates. The Bishop score rates dilatation, length (effacement), station, consistency and position.
- Ferguson reflex: stretching of the cervix and vagina releases oxytocin, which strengthens contractions (positive feedback).
- Tocolysis: atosiban blocks myometrial oxytocin receptors; nifedipine blocks Ca²⁺ channels; indomethacin inhibits prostaglandins but risks premature closure of the ductus after 32 weeks.
- Third stage: oxytocin reduces postpartum haemorrhage by contracting the uterus and compressing spiral vessels.
Lactation
- During pregnancy, oestrogen and progesterone develop ducts and alveoli but block milk secretion; after the placenta is delivered they fall and prolactin starts lactation.
- Prolactin (anterior pituitary) drives milk synthesis; suckling releases it; hypothalamic dopamine inhibits it.
- Oxytocin (posterior pituitary) causes milk ejection (let-down) by contracting myoepithelial cells; triggered by suckling and even the baby's cry.
- Lactational amenorrhoea: prolactin and suckling disrupt GnRH pulses, suppressing LH and FSH.
- Colostrum is rich in secretory IgA, which protects the infant's gut (only IgG crosses the placenta), protein and immune cells, but low in fat.
- Breast milk is low in vitamin K (newborns get it at birth) and vitamin D: exclusively breastfed babies, especially of mothers who stay indoors or cover fully, need vitamin D 400 units daily.
- Sheehan syndrome: the pituitary enlarges in pregnancy (lactotroph hyperplasia) while its blood supply is from low-pressure portal veins, so massive postpartum haemorrhage with hypotension infarcts it. Failure of lactation is the first sign, then amenorrhoea and hypopituitarism (check cortisol before giving thyroxine).
Remember hCG rescues the corpus luteum; the placenta takes over by 10 weeks; prolactin makes milk and oxytocin ejects it.
Exam trap Pregnancy causes a compensated respiratory alkalosis with low PaCO₂, low urea and creatinine, and normal free T4.
Exam trap A raised ALP in late pregnancy is normal (placental), but a raised ALT or bilirubin is not.
How FCPS asks about this
- Best test before a missed period: serum β-hCG; doubles every 48 hours in a normal pregnancy.
- Source of oestrogen and progesterone after 10 weeks: placenta.
- Faint and hypotensive supine at 34 weeks: aortocaval compression; turn to the left.
- Pyelonephritis in pregnancy: progesterone-dilated ureters and urinary stasis.
- Atosiban: oxytocin receptor antagonist; dinoprostone remodels cervical collagen.
- Antibody in colostrum: secretory IgA; breast milk lacks vitamins K and D.
- Failure of lactation after massive PPH: Sheehan syndrome; enlarged pituitary on low-pressure portal supply.
Test yourself on this topic
5 of the 200 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A woman at 36 weeks needs an emergency operation under general anaesthesia. The anaesthetist uses rapid sequence induction with cricoid pressure. Which change of pregnancy most increases her risk of aspirating gastric contents?
Answer: Progesterone relaxes the LOS
Progesterone relaxes smooth muscle throughout the body, including the lower oesophageal sphincter, so its tone falls during pregnancy. At the same time the enlarging uterus raises intra-abdominal pressure and displaces the stomach upwards, distorting the gastro-oesophageal angle. Heartburn is therefore common, and regurgitation with aspiration is a major risk under anaesthesia. Antacid prophylaxis, an H2 blocker and rapid sequence induction are used to reduce it.
Aspiration risk in pregnancy
- Progesterone relaxes the LOS
- Uterus raises abdominal pressure
- Common heartburn
- Use rapid sequence induction
Remember Every pregnant patient past mid-pregnancy has a 'full stomach'.
Exam trap Aspiration of acid gastric contents under anaesthesia is called Mendelson syndrome.
Why the other options are wrong
- hCG increases gastric acid secretion hCG does not raise acid secretion.
- Oestrogen speeds up gastric emptying Gastric emptying is not speeded up; in labour it is delayed.
- Relaxin tightens the pyloric sphincter Relaxin acts on pelvic ligaments, not the pylorus.
- Prolactin increases gastric volume Prolactin acts on the breast, not on gastric volume.
A woman with a BMI of 33 and a previous large baby is pregnant. When is she usually offered a 75 g oral glucose tolerance test to look for gestational diabetes?
Answer: At 24–28 weeks
Insulin resistance rises through pregnancy because of placental hormones such as hPL, so gestational diabetes usually appears in the second half. Women with risk factors (obesity, previous macrosomic baby or GDM, family history, South Asian ethnicity) are offered a 75 g OGTT at 24–28 weeks (earlier as well if previous GDM). HbA1c is not reliable for diagnosing GDM.
Gestational diabetes screening
- Risk factors: obesity, big baby, South Asian
- 75 g OGTT at 24–28 weeks
- Earlier if previous GDM
- HbA1c unreliable in pregnancy
Remember Mid-pregnancy is when GDM shows.
Exam trap Women with GDM have a high lifetime risk of type 2 diabetes.
Why the other options are wrong
- At 6 weeks only Too early to catch most GDM.
- At 36 weeks Too late to prevent complications.
- Only after delivery Misses the pregnancy.
- Never; HbA1c is enough Not reliable in pregnancy.
A woman at 34 weeks has painless, bright red vaginal bleeding. The uterus is soft and non-tender and the fetal head is high. What is the most likely diagnosis, and what must be avoided?
Answer: Placenta praevia; no vaginal exam
Placenta praevia: painless, recurrent bright red bleeding; soft non-tender uterus; malpresentation or high head. Digital examination can provoke torrential bleeding. Abruption: painful bleeding, tense 'woody' uterus, fetal distress, DIC risk. Vasa praevia: bleeding at membrane rupture with fetal bradycardia (fetal blood).
Antepartum haemorrhage
- Praevia: painless, soft uterus, no PV exam
- Abruption: painful, woody uterus, DIC
- Vasa praevia: fetal bleeding at ROM
Remember Praevia painless; abruption agony.
Why the other options are wrong
- Abruption; give oxytocin Abruption is painful with a tense uterus.
- Vasa praevia; perform amniotomy Vasa praevia bleeds at membrane rupture; amniotomy is dangerous.
- Uterine rupture; examine vaginally Rupture: pain, shock, fetal parts palpable.
- Cervical ectropion; reassure only Wrong diagnosis.
A woman at 30 weeks is carrying a fetus with anencephaly, which is accompanied by marked fetal adrenal hypoplasia. Her serum oestriol is very low, while hCG and progesterone are in the normal range. Which of the following explains the low oestriol?
Answer: Fetal adrenal DHEA-S is its main precursor
The placenta cannot make oestrogens from cholesterol because it lacks 17α-hydroxylase. The fetal adrenal zone makes large amounts of DHEA sulphate, which the fetal liver 16α-hydroxylates; the placenta then removes the sulphate and aromatises it to oestriol. Without a functioning fetal adrenal, as in anencephaly, oestriol falls sharply. Progesterone is made by the placenta from maternal cholesterol, so it stays normal.
Fetoplacental unit
- Placenta lacks 17α-hydroxylase
- Fetal adrenal makes DHEA-S
- Fetal liver 16α-hydroxylates
- Placenta makes oestriol
Remember Oestriol needs the fetus; progesterone does not.
Exam trap Low oestriol with normal fetus can occur in placental sulphatase deficiency.
Why the other options are wrong
- The placenta lacks aromatase in anencephaly Placental aromatase is normal.
- Maternal ovaries stop making oestrogen The ovaries make little oestrogen after early pregnancy.
- Maternal adrenal androgens are its main source Maternal androgens supply only a small fraction of oestriol.
- The fetal kidney fails to excrete oestriol Oestriol is measured in maternal blood; fetal kidneys are not the issue.
In a healthy woman at 32 weeks, minute ventilation has risen by about 40% while her respiratory rate is unchanged. Which change accounts for this?
Answer: Larger tidal volume
Progesterone increases the sensitivity of the respiratory centre to CO₂, so ventilation rises from early pregnancy. The increase comes almost entirely from a larger tidal volume, about 30–40% more, with little change in rate. PaCO₂ falls to about 4 kPa (30 mmHg), with renal compensation. As the uterus raises the diaphragm, FRC falls by about 20%, which is why pregnant women desaturate quickly during apnoea.
Breathing in pregnancy
- Progesterone: more CO₂ sensitivity
- Tidal volume up 30–40%
- Rate unchanged
- FRC falls about 20%
Remember Deeper, not faster.
Exam trap A non-pregnant normal PaCO₂ of 5.3 kPa in late pregnancy may signal respiratory compromise.
Why the other options are wrong
- Faster respiratory rate The rate barely changes.
- Larger functional residual capacity FRC falls as the diaphragm rises.
- Larger residual volume Residual volume falls slightly.
- Larger anatomical dead space Dead space changes little.
Where this sits in the CPSP syllabus
- Paper 1: Reproduction, Pregnancy, placental hormones, parturition and lactation
- Surgery & Allied, Paper 2: Reproduction, Pregnancy, placental hormones, parturition and lactation
- Medicine & Allied, Paper 2: Reproduction, Pregnancy, placental hormones, parturition and lactation
Read next
Drug dose pages
Doses, cautions and practical tips for drugs in this chapter.