37 Placental function

Question 1

Which of the following are able to cross the placenta?
A. Amino acids
B. alcohol 
C. Toxoplasma 
D. Rubella and herpes virus 
E. Heparin 
F. Zika virus 
G. H5N1

Answer 1

All except E

Non-transferable substances: some bacteria, heparin, transferrin, IgS, IgM (larger than size of IgG)
- H1N1 and H7N9 cannot cross

Can cross:

• Syphilis that causes sexually transmitted disease
• A number of viruses (e.g. rubella, cytomegalovirus, herpes)
• An intracellular parasitic protozoan (e.g. Toxoplasma gondii
• H5N1, Zika virus

Question 2

List the 3 facilitating factors for O2 transfer from maternal to fetal circulation down a gradient of 25 mmHg.

Answer 2

1. Higher affinity of fetal Hb for O2 than adult Hb (= same partial pressure of O2, fetal Hb can get saturated to higher percentage)
2. Higher Hb concentration in fetal blood
3. Double Bohr effect

§ Rightward shift of maternal HbA-O2 dissociation curve due to fall in pH and rise in CO2 maternal blood from uptake of fetal CO2
§ Leftward shift of fetal HbF-O2 curve due to rise in fetal blood pH and unloading of CO2
§ Umbilical vein (to fetus) blood: oxygenated; arterial blood: deoxygenated

Question 3

List a facilitating factor for CO2 transfer from fetal to maternal circulation down a gradient of 25 mmHg.

Answer 3

Facilitated by double Haldane effect - deoxygenated Hb has higher affinity for CO2 than oxygenated Hb

• Fetal: as HbF becomes more oxygenated, HbF affinity for CO2 decreases, promoting unloading of CO2 from HbF
• Maternal: as more O2 is unloaded from HbA, affinity of deoxygenated HbA to CO2 increases (CO2 is then picked up by maternal blood)

Question 4

The permeability of placental barrier is mainly determined by the _______________.

Answer 4

syncytiotrophoblast

Question 5

Can IgG antibodies cross the placenta? Why?

Answer 5

Protective IgG antibodies can cross the placenta, thus providing passive immunity to the fetus/newborn

because of
○ Size of molecules
○ Presence of IgG-specific carrier for active placental transport
○ Transfer by pinocytosis (3rd trimester)

Question 6

What maternal antibodies cannot cross the placenta?

Answer 6

• IgM for ABO blood group antigens

- Allergy-producing IgE, IgA

Question 7

Placenta as a barrier to hormones:

A. Insulin is used for the treatment of DM in pregnant women
B. Oral-anti-diabetic drugs are contraindicated for fear of possible teratogenicity and hypoglycemia in neonates

C. Synthetic glucocorticoids such as betamethasone and dexamethasone are given before birth (antenatally) to speed up lung maturation of a preterm fetus (+ delay premature labour for more time for maturation)

D. Cortisol can be administered directly to pregnant women

Answer 7

All except D

Question 8

What is the function of 5-deiondinase?

Answer 8

To convert T4 to reverse T3

Question 9

Which of the following is correct?
A. Only 5-deiodinase but not 5’-deiodinase is present in the placenta

B. Although 5-deiodinase reduces the transfer of maternal T4 to fetus, maternal T4 crosses the placenta in significant quantity

C. Maternal T4 to fetus is important for embryogenesis and maturation of fetal CNS before the fetal thyroid axis becomes functional late in 1st trimester

D: during the 2nd and 3rd trimester, maternal T4 is no longer important

Answer 9

B and C only

A: Both 5-deiodinase and 5’-deiodinase are present in the placenta

D: During the 2nd and 3rd trimester, small amounts of T4 transfer contribute to the crucial fetal requirement of thyroid hormones for growth and brain development

Question 10

Which of the following is correct?

A. Dietary insufficiency of thyroid hormones in pregnant mothers give rise to neonatal hypothyroidism > neurodevelopmental deficits

B. Pregnant mothers with thyrotoxicosis will cause direct problems to the fetus

C. Grave’s disease will not cause a problem to the fetus

D. Anti-thyroid drugs can cross the placenta and will affect fetal thyroid function

Answer 10

A and D only

B: Do not pose a direct problem to the fetus due to the presence of placental 5-deiodinase (convert T4 to rT3)

§ However, uncontrolled hypermetabolic state of mother is associated with numerous adverse outcomes

1. Increase in neonatal mortality rate
2. Delivery of low birth weight infants
3. Risk of premature labour and preeclampsia

C: Thyroid stimulating immunoglobulin (TSI:IgI) can cross the placenta causing hyperthyroidism in fetus

D: will produce a teratogenic effect

Question 11

List the 2 main antithyroid drugs and briefly describe how to administer these drugs.

Answer 11

1. propylthiouracil/PTU
2. carbimazole/ methimazole

PTU: higher binding to serum albumin is preferred in first trimester (period of organogenesis) due to less placental transfer > later switch to CMZ/MMI since chronic use of PTU may increase incidence of hepatitis

Question 12

What are the side effects of CMZ (carbimazole)/ MMI (methimazole) ?

Answer 12

scalp defect/aplasia cutis congenita: congenital absence of skin in a localized/widespread area

Question 13

Pregnancy test is based on the detection of?

Answer 13

human chorionic gonadotrophin (hCG):

in maternal blood soon after implantation

Question 14

Human chorionic gonadotrophin (hCG):

A. is considered to have caused “morning sickness”
B. is considered to have caused hyperemesis gravidarum (persistent vomiting, weight loss of > 5%, ketonuria, electrolyte abnormalities like hypokalemia, dehydration: high urine specific gravity)
C. is thyrotropic = stimulates maternal thyroid gland activity
D. is prolactin-like to affect mammary gland
E. is GH-like to induce insulin resistance in the mother

Answer 14

All of the above

E: diabetogenic effect:
insulin resistance> spare glucose for fetal use, will cause gestational diabetes;
stimulate lipolysis

Question 15

Human placental lactogen rise is inversely related to the placental mass.
T/F?

Answer 15

False

Human placental lactogen rise parallels to the increase in placental mass (in the past: marker for twin pregnancy)

Question 16

When is the peak value of Human chorionic gonadotrophin (hCG)?

Answer 16

9-10 weeks

Question 17

What are the sources of progesterone? In which period of pregnancy are they involved in?

Answer 17

1. Corpus luteum: luteal phase of pregnancy (7-9th week)
2. Placenta: placental phase of pregnancy (7-9th week of pregnancy to term)

Pregnancy can proceed in the absence of ovary after reaching the placental phase *due to placental secretion of progesterone

Question 18

Which of the following is true about the effects of progesterone?

A. It prepares endometrium to attain optimal receptivity for implantation to occur together with estradiol

B. It stimulates secretory changes of the endometrium in the luteal phase to provide nutritional support to pre-implantation embryo

C. It inhibits myometrial smooth muscle contraction

D. It stimulates lobulo-alveolar growth and differentiation of the mammary gland

E. It promote an increase in ventilation rate

F: It prevents Conn’s syndrome

G: It prevents Cushing’s syndrome

Answer 18

All of the above

C:

It inhibits myometrial smooth muscle contraction for implantation to occur and pregnancy to be maintained

D: It promote an increase in ventilation rate through resetting the respiratory center to higher sensitivity to CO2

F: Counteract the aldosterone effect in salt and fluid retention (prevent Conn’s syndrome)

G: Counteract the effects of elevated plasma cortisol levels in the mother (prevent Cushing’s)

Other effects not mentioned:
1. Inhibit the maternal pituitary gonadotrophin secretion (tgt with estrogens), thus preventing a new cycle of follicular development > secondary amenorrhea

2. Together with estrogens, stimulate uterine growth during pregnancy
3. Antagonize the pressor effect of angiotensin II due to its smooth muscle relaxant effect

Question 19

What are the sources of estrogen?

How does the amount of estrogen change along pregnancy?

Answer 19

1. Corpus luteum
2. Feto-placental unit (estriol: main estrogen formed during pregnancy)

With the maturation of fetal-adrenal axis, estrogen production increases to promote the onset of labor

Question 20

List the 6 main functions of estrogen.

Answer 20

1. Stimulate stromal and ductular growth of mammary gland
2. Stimulate uterine growth resulting in hypertrophy and hyperplasia of uterine smooth muscles
3. Stimulate prostaglandin synthesis to initiate parturiton
4. Stimulate prolactin secretion from anterior pituitary gland > hyperplasia and hypertrophy of lactotrophs
5. Inhibit maternal pituitary gonadotrophin secretion
6. Stimulate hepatic production of hormone binding proteins (TBC and CBG), leading to increased maternal plasma levels of total T4 and cortisol

Question 21

In pregnant women,

A. both bound and free form of cortisol increases

B: insulin resistance and appearance of striae are signs of hypercorticolism

C: increased cortisol is for promoting lipogenesis

D: increased cortisol is for decreasing protein synthesis and stimulating proetolysis

Answer 21

All except C

A is correct: Bound cortisol: increased CBG production under estrogen stimulation
Free cortisol: displacement of cortisol binding to CBG by high levels of progesterone; stimulation of maternal ACTH-cortisol by placental CRH

C: promote lipolysis: provide free fatty acids and ketones as alternative metabolic fuel for maternal and fetal use

D: provide substrate for gluconeogenesis

Question 22

Relaxin:

A. is produced by the placenta only

B. causes relaxation of the interpubic ligament

C. Act synergistically with progesterone to inhibit myometrial motility

D.Involve in the remodeling of the uterus

E. Stimulate cervical ripening by inhibiting collagen synthesis

F. Is a member of insulin-like gene

Answer 22

All except A

Produced by the corpus luteum, placenta and myometrium