Placental and fetal growth and development

The villus

Despite the arrangement of villi into maternal cotyledons, the functional unit of the placenta remains the stem villus or fetal cotyledon . The end unit of the stem villus, sometimes known as the terminal or chorionic villus, is shown in Fig. 4.4 . There are initially about 200 stem villi arising from the chorion frondosum. About 150 of these structures are compressed at the periphery of the maternal cotyledons and become relatively functionless, leaving a dozen or so large cotyledons and 40–50 smaller ones as the active units of placental function.

The estimated total surface area of the chorionic villi in the mature placenta is approximately 11m ² . The surface area of the fetal side of the placenta and of the villi is enlarged by the presence of numerous microvilli. The core of the villus consists of a stroma of closely packed spindle-shaped fibroblasts and branching capillaries. The stroma also contains phagocytic cells known as Hofbauer cells . In early pregnancy, the villi are covered by an outer layer of syncytiotrophoblast and an inner layer of cytotrophoblast. As pregnancy advances, the cytotrophoblast disappears until only a thin layer of syncytiotrophoblast remains. The formation of clusters of syncytial cells, known as syncytial knots, and the reappearance of cytotrophoblast in late pregnancy are probably the result of hypoxia. There is evidence that the rate of apoptosis of syncytial cells accelerates towards term and is particularly increased where there is evidence of fetal growth impairment.

Structure of the umbilical cord

The umbilical cord contains two arteries and one vein ( Fig. 4.5 ). The two arteries carry deoxygenated blood from the fetus to the placenta and the oxygenated blood returns to the fetus via the umbilical vein. Absence of one artery occurs in about 1 in 200 deliveries and is associated with a 10–15% incidence of cardiovascular anomalies. The vessels are surrounded by a hydrophilic mucopolysaccharide known as Wharton’s jelly, and the outer layer covering the cord consists of amniotic epithelium. The cord length varies between 30 and 90cm.

The vessels grow in a helical shape. This configuration has the functional advantage of protecting the patency of the vessels by absorbing torsion without the risk of kinking or snarling of the vessels.

The few measurements that have been made in situ of blood pressures in the cord vessels indicate that the arterial pressure in late pregnancy is around 70mmHg systolic and 60mmHg diastolic, with a relatively low pulse pressure and a venous pressure that is exceptionally high, at approximately 25mmHg. This high venous pressure tends to preserve the integrity of the venous flow and indicates that the pressure within the villus capillaries must be in excess of the cord venous pressures.

The cord vessels often contain a false knot consisting of a refolding of the arteries; occasionally, blood flow is threatened by a true knot, although such formations are often seen without any apparent detrimental effects on the fetus.

In the full-term fetus, the blood flow in the cord is approximately 350mL/min.

Factors that regulate fetoplacental and uterine blood flow

The fetoplacental circulation is affected by the fetal heart and aorta, the umbilical vessels and the vessels of the chorionic villi, so factors that affect these structures may affect the fetal circulation. Such factors as oedema of the cord, intramural thrombosis and calcification within the large fetal vessels or acute events such as acute cord compression or obstruction of the umbilical cord may have immediate and lethal consequences for the fetus. However, the more common factors that influence the welfare of the fetus arise in the uteroplacental circulation. Access to these factors by the use of Doppler ultrasound has greatly improved our understanding of the control mechanisms of uterine blood flow.

The regulation of uterine blood flow is of critical importance to the welfare of the fetus. The uteroplacental blood flow includes the uterine arteries and their branches down to the spiral arterioles, the intervillous blood flow and the related venous return.

Impairment of uterine blood flow leads to fetal growth impairment and, under severe circumstances, to fetal death. Factors that influence uteroplacental blood flow acutely include maternal haemorrhage, tonic or abnormally powerful and prolonged uterine contractions and substances such as noradrenaline (norepinephrine) and adrenaline (epinephrine). Angiotensin II increases uterine blood flow at physiological levels, as it has a direct effect on the placental release of vasodilator prostaglandins, but in high concentrations it produces vasoconstriction.

At the simplest level, acute fetal asphyxia can be produced by the effect of the mother lying in the supine position in late pregnancy, causing compression of the maternal inferior vena cava and hence a sudden reduction in blood flow through the uteroplacental bed.

In terms of chronic pathology, the main causes of impaired uteroplacental circulation are inadequate trophoblast invasion and acute atherosis affecting the spiral arterioles, resulting in placental ischaemia, advanced maturation and placental infarction.

Simple diffusion

Transfer between maternal and fetal blood is regulated by the trophoblast, and it must be remembered that the layer separating fetal from maternal blood in the chorionic villus is not a simple semipermeable membrane but a metabolically active cellular layer. However, with regard to some substances, it does behave like a semipermeable membrane, and substances pass by simple diffusion.

Although there are some exceptions, small molecules generally cross the placenta in this way, and movement is determined by chemical or electrochemical gradients. The quantity of solute transferred is described by the Fick diffusion equation:

where $\text{Q}/t$ is the quantity transferred per unit of time, K is a diffusion constant for the particular substance, A is the total surface area available, C ¹ and C ² indicate the difference in concentrations of solute and L represents the thickness of the membrane.

This method is applicable particularly to transfer of gases, although the gradient of oxygen, for example, is exaggerated by the fact that oxygen is extracted by the villous trophoblast.

Facilitated diffusion

Some compounds are transported across the placenta at rates that are considerably enhanced above the rate that would be anticipated by simple diffusion. Transport always occurs in favour of the gradient, but at an accelerated rate. This mechanism pertains to glucose transport and can only be explained by the active involvement of enzyme processes and specific transport systems.

Active transport

Transfer against a chemical gradient occurs with some compounds and must involve an active transport system that is energy dependent. This process occurs with amino acids and water-soluble vitamins and can be demonstrated by the presence of higher concentrations of the compound in the fetal blood as compared with maternal blood. Such transfer mechanisms can be inhibited by cell poisons and are stereo-specific.

Pinocytosis

Transfer of high-molecular-mass compounds is known to occur even where such transfer would be impossible through the villus membrane because of the molecular size. Under these circumstances, microdroplets are engulfed into the cytoplasm of the trophoblast and then extruded into the fetal circulation. This process applies to the transfer of globulins, phospholipids and lipoproteins and is of particular importance in the transfer of immunologically active material. The major source of materials for protein synthesis, which also accounts for some 10% of energy supplies, is amino acids transferred by active transport.

Transport of intact cells

Fetal red cells are commonly seen in the maternal circulation, particularly following delivery. This transfer occurs through fractures in the integrity of the trophoblastic membrane and may also therefore occur at the time of abortion or following placental abruption. Although some maternal cells can be found in the fetal circulation, this is much less common. As previously mentioned, the pressure gradient favours movement from the relatively high pressure of the fetal capillaries to the low-pressure environment of the intervillous space.

Water and electrolyte transfer

Water passes easily across the placenta, and a single pass allows equilibrium. The driving forces for movement of water across the placenta include hydrostatic pressure, colloid osmotic pressure and solute osmotic pressure.

Gaseous exchange

As the transfer of gases occurs by simple diffusion, the major determinants of gaseous exchange are the efficiency and flow of the fetal and maternal circulation, the surface area of the placenta that is available for transfer and the thickness of the placental membrane.

Oxygen transfer

The average oxygen saturation of maternal blood entering the intervillous space is 90–100% at a P o ₂ of 90–100mmHg, and these high levels of oxygen favour transfer to the fetal circulation. After the placenta itself has utilized some of this oxygen, the remainder is available to the fetal circulation. Fetal haemoglobin has a higher affinity for oxygen than does adult haemoglobin, and haemoglobin concentration is higher in the fetus. All of these factors favour the rapid uptake of oxygen by the fetus at P o ₂ levels as low as 30–40mmHg. The extent to which haemoglobin can be saturated by oxygen is affected by hydrogen ion concentration. The increase that occurs in deoxygenated blood arriving in the placental circulation from the fetus favours the release of maternal oxygen in the fetoplacental bed. The oxygen dissociation curve is shifted to the right by the increase in H ⁺ concentration, P co ₂ and temperature, and this is known as the Bohr effect ( Fig. 4.8 ). Oxygen is predominantly transported in the form of oxyhaemoglobin, as there is little free oxygen in solution.