Maternal Changes in Pregnancy (Physiology 2)

The implantation window occurs 6 to 10 days after the LH spike.

Pre-decidualization occurs during the implantation window.

Endometrial cells become modified, filled with lipids and glycogen, and cover the surface of the uterus.

These modified cells become the maternal contribution to the placenta if pregnancy occurs.

Growth factors

Adhesion molecules

Nutrients

Vitamins, matrix proteins, and hormones

The syncytiotrophoblast is formed by cell fusion, creating a multi-nucleated cytoplasmic mass.

It invades the endometrium.

The syncytiotrophoblast erodes the endometrium.

Cells of the embryonic disc form epiblast and hypoblast.

The epiblast develops a fluid-filled amniotic cavity.

Implantation is complete as the extraembryonic mesoderm forms a discrete layer beneath the cytotrophoblast.

The blastocyst is at the 12-day stage.

The cytotrophoblast and associated mesoderm form the chorion.

The chorionic villi begin to extend.

Lacunae fill with maternal blood, which mingles with the villi.

The maternal-fetal interface refers to the area where the maternal and fetal tissues meet, facilitating nutrient and gas exchange.

It consists of the placenta, which serves as a barrier between the mother and fetus.

The interface is responsible for the exchange of oxygen, nutrients, waste, and hormones between the maternal and fetal circulations.

Human chorionic gonadotrophin (hCG) is secreted by the syncytiotrophoblast and increases rapidly during pregnancy.

hCG binds to LH receptors to prevent the death of the corpus luteum, ensuring continued production of estrogen and progesterone.

This hormonal shift triggers rapid changes in maternal systems in response to luteal and later placental steroids.

Serum hCG levels are maximal between 9 and 11 weeks of pregnancy.

hCG is useful for monitoring early pregnancy complications, such as ectopic pregnancy or miscarriage.

Placental steroidogenesis is the synthesis of steroids derived from fetal and maternal adrenals.

The placenta lacks 17α-hydroxylase and 17,20 lyase enzymes.

Progesterone:

Synthesized directly from cholesterol.

Responsible for decidualization, smooth muscle relaxation, mineralocorticoid effects, and breast development.

Estrogens (Estradiol and Estriol):

Contribute to uterine hypertrophy, metabolic changes, cardiovascular effects, increased clotting factor production, and breast development.

Total weight gain: 9-13 kg

Foetus and placenta: 5 kg

Fat and protein: 4.5 kg

Body water: 1.5 kg

Breasts: 1 kg

Uterus: 0.5-1 kg

Approximately 2.0 kg in the first 20 weeks.

Then, weight gain continues at about 0.5 kg per week until full term at 40 weeks.

Total weight gain during pregnancy: 9-13 kg.

Failure to gain or sudden changes in weight should be investigated.

Constant weight monitoring can cause anxiety.

Weight gain failure or sudden changes require investigation.

BMR rises by 350 kcal/day during mid gestation.

BMR rises by 250 kcal/day during late gestation.

75% of the increased caloric expenditure goes to the foetus and uterus.

25% is used for respiration.

Glucose is transported across the placenta to provide foetal energy.

Increased blood glucose levels occur during the 2nd trimester.

Maternal reserves are primarily used for energy.

Pancreatic cells increase in number, raising circulating insulin.

Fasting serum glucose decreases as more glucose is taken up into tissues.

Foetal reserves are emphasized for energy.

Placental lactogen causes insulin resistance, meaning less glucose is stored.

This leads to an increase in serum glucose in the mother.

Foetus

Placenta

Amniotic fluid

Oedema (swollen ankles, connective tissue, lungs)

Uterine muscle

Breasts

Plasma volume

Estrogen and progesterone act like mineralocorticoids, causing increased sodium retention by the kidneys.

This leads to an increase in blood volume.

RAAS: Placental renin production and angiotensinogen synthesis by the liver increase.

Angiotensin II and aldosterone are elevated.

Progesterone decreases vaso-sensitivity, leading to resistance to AT2 receptor-mediated vasoconstriction, despite higher levels of angiotensin II.

Connective tissue and ligaments take on water, becoming softer.

Resetting of the osmostat decreases the thirst threshold.

Decrease in oncotic pressure (due to lower albumin levels).

Up to 8.5 liters of total water gain.

Increased efficiency of iron absorption from the gut to meet maternal and fetal needs.

Circulating blood volume increases from 4.5 to 6.0 liters.

Haemodilution refers to the apparent anaemia that occurs as the concentration of hemoglobin (Hb) falls, due to the increase in plasma volume.

Increase in white blood cells and clotting factors.

Blood becomes hypercoagulable, increasing the risk of clot formation.

Increase in fibrinogen is essential for placental separation, but also raises the risk of thrombosis.

The expanding uterus can put pressure on the heart, potentially altering ECG and heart sounds.

Peripheral vasodilation occurs due to progesterone reducing smooth muscle intracellular calcium and estrogen inducing NO synthase in vascular endothelium.

Total peripheral resistance (TPR) falls by 20-30%.

Cardiac output (CO) increases, leading to a slight decrease in blood pressure (BP) during the first two trimesters.

There is an increase in cardiac output, with stroke volume and heart rate rising, reaching a maximum of 40% at 28 weeks.

These changes begin as early as 3 weeks into pregnancy.

Increased cardiac output can exacerbate pre-existing conditions, such as aortic valve defects or pulmonary hypertension

Increased cardiac output and vasodilation are induced by steroids.

This leads to reduced peripheral resistance and increased blood flow to key organs.

Uterus

Placenta

Muscle

Kidneys

Skin

Neoangiogenesis refers to the formation of new blood vessels.

This includes the development of extra capillaries in the skin, resulting in spider naevi, which assist with heat loss.

Pregnancy is characterized by low blood pressure and high blood volume.

Progesterone binds to smooth muscle receptors in the GI tract, resulting in lower intracellular calcium levels.

This leads to muscle relaxation in the GI tract.

Estrogen plays a lesser role compared to progesterone.

It induces nitric oxide synthetase, which synergizes with progesterone's effects on the GI tract.

DNA production and growth of blood cells.

Supports the foetus, placenta, and uterus.

Essential for the proper development of the neural tube.

Supplementation is advised up to 400μg/day until week 12 of pregnancy.

Ideally, supplementation should start 3 months before pregnancy.

Deficiency can lead to birth defects, such as spina bifida and other neural tube defects.

Relaxin from the corpus luteum/placenta stimulates the formation of endothelial nitric oxide synthetase.

This enzyme mediates the dilation of renal arteries through nitric oxide.

Progesterone and relaxin cause resistance to angiotensin II-mediated vasoconstriction, leading to further vasodilation.

These changes increase renal blood flow and glomerular filtration rate (GFR).

Placental CRH is released into both maternal and foetal circulation.

Placental CRH stimulates the release of cortisol through a positive feedback mechanism.

Cortisol causes metabolic changes, such as insulin resistance, in the mother.

Cortisol promotes foetal lung maturity and has mineralocorticoid actions (similar to aldosterone).

Cortisol increases the production of prostaglandin E2 and oxytocin by the placenta.

DHEA, produced in the foetal adrenal glands, is aromatized into estrogen by the placenta.

The increase in the estrogen-to-progesterone (E:P) ratio stimulates the production of prostaglandins, which enhance blood flow, uterine contractions, and cervical ripening.

The patient may require endocrine management to maintain normal thyroid function.

Biochemical tests may indicate hyperthyroidism, but the patient may actually be normal, particularly in the case of gestational thyrotoxicosis.

Anxiety

Tremor

Heat intolerance

Palpitations

Weight loss or lack of weight gain

Goiter, tachycardia, and hyperreflexia (often associated with hyperemesis gravidarum).

Suppressed TSH and high serum T4.

Increased thyroid hormone production to meet the increased metabolic demand of pregnancy may lead to gestational thyrotoxicosis.

hCG may act on the TSH receptor, leading to increased thyroid hormone production.

T4 is the major form, and it has a longer half-life than T3.

T4 is converted to the active form, T3.

The hypothalamus releases TRH, which stimulates the pituitary to release TSH, leading to the production of T4 and T3 by the thyroid.

There is a large increase in muscle mass during the first 20 weeks, ranging from 50g to 1000g.

At 12 weeks, the uterine fundus may be palpated through the abdomen above the symphysis pubis.

The uterus reaches its peak size at 36 weeks.

Stretching

Increased blood flow

The primary function of the cervix is to retain the pregnancy.

Tissue softening of the cervix begins at 8 weeks.

There are changes in connective tissue that prepare the cervix for expansion.

There is proliferation of glands, and the mucosal layer becomes half of the cervix's mass.

There is a great increase in mucus production, which serves a protective (anti-infective) role.

Pituitary

Myometrium

Placenta

Sex steroids inhibit the stimulatory effects of prolactin on milk production.

The abrupt drop in steroid levels following placental delivery allows existing prolactin to induce lactation.

Suckling activates nipple mechanoreceptors, signaling the hypothalamus and causing anterior pituitary prolactin secretion.

Stretching of the uterus and cervix during childbirth causes the release of oxytocin.

Oxytocin helps with birth and plays a role in emotional bonding with the baby.

Suckling stimulus triggers the release of oxytocin from the posterior pituitary gland, leading to milk ejection.

Prolactin controls milk production.

Oxytocin controls the milk-ejection reflex.

There is a dramatic and rapid fall in steroids upon delivery of the placenta.

Most endocrine-driven changes return to normal rapidly.

Uterine muscle rapidly loses oedema but contracts slowly.

However, it does not return to pre-pregnancy size.

The removal of steroids allows the action of raised prolactin on milk production.

Cardiac output (CO) increases by 30-40% due to increased stroke volume and heart rate.

Total peripheral resistance (TPR) decreases by 20-30% due to vasodilation.

Blood pressure (BP) slightly decreases in the first two trimesters but may return to baseline levels by the third trimester.

Increased blood volume and pressure from the growing uterus can lead to poor venous return, contributing to varicose veins and oedema, especially in the legs.

Hormonal changes, such as increased progesterone, cause relaxation of smooth muscle in blood vessels, further exacerbating venous pooling.

Tidal volume increases by 30-40%, allowing for greater lung expansion.

Respiratory rate may remain the same or slightly increase.

These changes improve oxygenation for both the mother and foetus and help meet the increased metabolic demands during pregnancy.

Progesterone relaxes the lower oesophageal sphincter, allowing stomach acid to reflux into the oesophagus.

The growing uterus applies pressure on the stomach, further contributing to acid reflux and heartburn.

The placenta produces human chorionic gonadotropin (hCG), progesterone, and estrogen to support pregnancy.

It also plays a role in synthesizing placental lactogen and corticotropin-releasing hormone (CRH), which regulate metabolic and immune responses during pregnancy.

Insulin resistance increases during pregnancy, particularly in the second and third trimesters.

This allows for increased blood glucose levels, providing more energy to the foetus.

The mother's body compensates by producing more insulin, which may lead to gestational diabetes in some cases.

Increased blood pressure and protein in the urine can be normal during pregnancy, complicating the diagnosis of preeclampsia.

Elevated blood sugar levels can be seen in normal pregnancy due to insulin resistance, which makes diagnosing gestational diabetes challenging.

Fluid retention and swelling may overlap with symptoms of preeclampsia, further complicating diagnosis.