Physiology of the placenta

Question 1

What type of placenta do humans have and what does this mean?

Answer 1

Humans have a villous hemochorial placenta, meaning that maternal blood comes in direct contact with fetal trophoblasts (but not fetal blood).

Question 2

What are the stages of placental development?

Answer 2

Pre-lacunar (days 6-8)
Lacunar/trabecular (days 9-12)
Villous (days 13-18)

Question 3

What occurs in the pre-lacunar stage?

Answer 3

There is no true placental tissue until implantation (6-7 days after conception).

• blastocyst attachment to the endometrium -> trophectoderm proliferates.
• Fusion of outer layer -> non-mitotic, multinucleated syncytiotrophoblasts.
• inner layer -> remains as single cells (cytotrophoblasts)
• cytotrophoblast cells proliferate, providing cells to the syncytium that invades the adjacent maternal tissue

Question 4

What happens in the lacunar/trabecular stage?

Answer 4

Vacuoles appear within the syncytiotrophoblasts and eventually fuse to form lacunae (lakes). This results in the formation of pillars, called trabeculae, by the syncytiotrophoblasts. The lacunae make first contact with the eroded endometrial capillaries, and some maternal erythrocytes may be observed within the lacunae. This is the region that will develop into the intervillous space. Implantation is complete at this point.

Question 5

What happens in the villous stage?

Answer 5

• appearance and development (in three stages) of chorionic villi.
• cytotrophoblasts proliferate and begin to invade up the trabecular (pillars of syntax cells)
• Primary villus: consists of a cytotrophoblast core surrounded by syncytiotrophoblasts
• Secondary villus: extraembryonic mesoderm grows into the cytotrophoblast, the villi become secondary villi.
• Tertiary villus: mesenchymal cells differentiate into blood vessels resulting in the formation of an arteriocapillary network within the villous.

Question 6

What are the two types of tertiary villi?

Answer 6

Floating villi (FV) and anchoring villi (AV) 
At the tip of the anchoring villi a column of cytotrophoblasts makes contact with the decidua.  From the cell column, cytotrophoblasts invade through the decidua to the inner 1/3 of the myometrium (interstitial invasion) and remodel the uterine spiral arteries

Question 7

What separates the maternal and fetal blood?

Answer 7

Fetal blood in the capillaries of the tertiary villi is separated from maternal blood surrounding the villi by a “placental membrane” composed of the capillary endothelium, mesenchyme, cytotrophoblast, and syncytiotrophoblast.

Question 8

What is the sequence of fetal circulation through the placenta?

Answer 8

• two umbilical arteries carry deoxygenated blood from the fetus to the placenta, branch, and dive through the chorionic plate.
• branch into arterioles, following the course of the villous tree and forming a capillary network within the chorionic villi.
• Maternal blood in the intervillous space provides oxygen to the fetal blood in the villi.
• The chorionic villi capillaries then form venules that ultimately connect to the umbilical vein, which carries oxygenated blood back to the fetus.

Question 9

What is a cotyledon and what is it’s overall structure?

Answer 9

Cotyledons are divisions in the maternal surface created by septa. Each cotyledon contains several main stem villi with many branching villi. The fetal capillary circulation (from the umbilical artery) runs throughout the inside of the villous structure, which is bathed in maternal blood from the maternal spiral arterioles.

Question 10

What are terminal villi and what is their function?

Answer 10

Terminal villi are grape-like structures located on tertiary villi that have many capillaries and highly-dilated sinusoids. Terminal villi are the locations where most of the villous growth and transplacental transport take place. This arrangement minimizes the transit distance between the fetal and maternal circulations.

Question 11

How is amniotic fluid produced in progressive stages of development?

Answer 11

Early in pregnancy, amniotic fluid is simply an ultrafiltrate of maternal plasma. Once the fetal kidneys start working (12 weeks), fetal urine becomes the major source. Late in pregnancy amniotic fluid is primarily fetal urine, with a small contribution from fetal lung secretions.

Question 12

What is oligohydramnios and what are some of its causes?

Answer 12

Oligohydramnios is a subnormal volume of amniotic fluid.

• most common cause is rupture of membranes.
• also maternal, placental, fetal, or drug causes.

Other etiologies lead to decreased volume by interfering with the production of amniotic fluid at multiple steps:

a. Maternal: poor placental perfusion due to pre-gestational diabetes, hypertension, preeclampsia
b. Placental: twin-twin transfusion
c. Fetal: congenital anomalies, particularly of the genitourinary system
d. Drugs: certain nephrotoxic medications (notably, prostaglandin synthase inhibitors and ACE inhibitors) can cause oligohydramnios by interfering with normal fetal renal function

Question 13

What is polyhydramnios and what are some causes?

Answer 13

Polyhydramnios (also called simply hydramnios) is a supernormal volume of amniotic fluid.

• congenital anomalies that interfere with fetal swallowing of amniotic fluid:
  
  • neural tube defects
  • esophageal atresia.
• Hydrops (fetal fluid excess secondary to hemolysis, congenital heart defect or infection) is another possible cause.
• diabetes.

Question 14

What mechanisms of transport are found in the placenta?

Answer 14

a. Diffusion: Transport across the placenta depends entirely on a concentration gradient between circulations. Examples: oxygen, carbon dioxide, water.
b. Facilitated diffusion: Transport is driven by a maternal-fetal concentration gradient, but requires specific carrier proteins. Example: glucose.
c. Active transport: Transport against the maternal-fetal concentration gradient, requiring energy expenditure. Example: amino acids

Question 15

What are the two types of placental transport behavior?

Answer 15

Diffusion-limited and flow-limited transport:

Substances subject to DIFFUSION-LIMITED TRANSPORT cross the placenta relatively slowly. The rate-limiting step is the rate of movement across the syncytiotrophoblast membranes between the intervillous space and the fetal capillaries. Therefore, the rate of transport is primarily influenced by the characteristics of the syncytiotrophoblast cell membrane. Example: oxygen.

For substances that cross the placenta more rapidly, transport is dependent on PLASMA CONCENTRATION and the RATE OF BLOOD FLOW. This FLOW-LIMITED TRANSPORT can be affected by several factors, including changes in uterine blood flow and therefore placental perfusion. For example, decreased maternal blood pressure→decreased uterine perfusion→decreased placental perfusion→decreased transport.

Question 16

What are examples of stresses resulting from defects in diffusion-limited or flow-limited transport?

Answer 16

i. Diffusion-limited: Direct damage to the syncytiotrophoblast will affect oxygen transport to the fetus.
ii. Flow-limited: Pregnant women with aortic stenosis have reduced cardiac output, which often leads to growth-restricted fetuses.

Question 17

How can the placenta be said to have hepatic function?

Answer 17

Drug metabolism occurs in the placenta:
The placenta is the primary barrier preventing fetal exposure to any drugs in the maternal circulation. It has functional capacity for drug metabolism (with enzymes for oxidation, glucuronidation, and sulfation). The safety of drugs in pregnancy is largely dependent on the ability of compounds to “cross the placenta.”

Question 18

How does the placenta function in temperature regulation?

Answer 18

Since normal cooling mechanisms are not available to the fetus, the placenta acts as a heat exchanger to maintain fetal temperature. Heat produced by fetal metabolic processes is removed by the maternal circulation. A clinical consequence of this is women reporting feeling warmer during pregnancy.

Question 19

What are the primary hormones created by the placenta?

Answer 19

Human chorionic gonadotropin (hCG)
Human placental lactogen (hPL)
large amounts of steroid hormones (e.g., estrogen and progesterone) that are critical to fetal well-being. Estrogenic precursors (i.e., progesterone and testosterone) are synthesized in the fetus and further processed by the placenta.

Question 20

What does hCG do?

Answer 20

hCG is made by trophoblast cells and maintains the corpus luteum, and therefore progesterone production. The earliest that the beta subunit of hCG can be found in the maternal plasma is 6-9 days post-conception.

Question 21

What does hPL do?

Answer 21

hPL is a counter-regulatory (anti-insulin) hormone. This is classically thought to contribute to the increased insulin resistance seen in pregnancy and development of gestational diabetes. Placental growth hormone is now thought to play a role in this process as well.

Question 22

What immunoglobulins may be present in a fetus, and what do they indicate?

Answer 22

1. The dominant fetal immune response is via IgM immunoglobulins. Since IgM is not transported across the placenta, any IgM found in fetal blood has been produced by the fetus, and may represent a response to a congenital infection.
2. In the absence of direct antigenic stimulus, the predominant immunoglobulin in the fetus is maternal IgG, which is transferred across the placenta. Transport of IgG to the Rh factor is what causes fetal immune hydrops in an Rh+ fetus in an isoimmunized Rh- mother.