Lecture 12: Placental Physiology and Developmental Disorders

Question 1

List functions of the placenta

Answer 1

Diffusion of oxygen and carbon dioxide

Diffusion of foodstuffs

Excretion of wast products

Question 2

Compare the early placenta with the late placenta

Answer 2

Early: Thick, Permeability low, Small surface area, Total diffusion conductance is miniscule

Late: Permeability high, Large surface area, Large increase in placental diffusion

Question 3

Describe the oxygen pressure gradient (near end of pregnancy) and explain why adequate oxygenation can occur with such a low pressure gradient

Answer 3

• pO₂ of mother = 50 mmHg
• pO₂ of fetus = 30 mmHg
• Hb can carry more oxygen at low pressures of carbon dioxide

Fetal hemoglobin has a higher affinity for oxygen and its hemoglobin concentration is about 50% greater than maternal… also the Bohr effect accounts for adequate oxygenation

Question 4

Describe the Bohr effect and the double Bohr effect

Answer 4

• Hb can carry more oxygen at low pCO₂
• Fetal blood coming into placenta carries more CO₂
• Excess CO₂ diffuses into maternal blood à fetal blood becomes more alkaline, maternal blood becomes more acidic
• Changes cause an increase in capacity of fetal blood to combine with oxygen and a decrease in capacity of maternal blood to combine with oxygen
• Double Bohr effect: refers to the shift in maternal/fetal blood oxygenation, helping to inc. fetal

Question 5

Human Chorionic Gonadotropin

Answer 5

• Secreted by the syncytial trophoblast cells into maternal fluids
• Measurable secretion 8-9 days after ovulation
• Maximal secretion during 10^th- 12^th week of pregnancy
• Lower levels secreted 16^th through 20^th weeks
• Functions:
  
  • Prevents involution of corpus luteum
  • Causes CL to increase secretion of progesterone and estrogens
  • Causes increase growth in CL
  • Exerts interstitial cell-stimulating effect on testes of male fetus—results in production of testosterone until birth

Question 6

Estrogens

Answer 6

• Secreted by syncytiotrophoblast cells of placenta
• Toward end of pregnancy, secretion level is 30x mother’s normal level
• Placental estrogens are formed almost entirely from androgenic steroid compounds
  
  • Formed in mother’s and fetus’ adrenal glands
  • Converted by trophoblast cells into estradiol, estrone, and estriol
• Functions:
  
  • Uterine enlargement
  • Breast enlargement
  • Growth of breast and ductal structure
  • Enlargement of maternal external genitalia
  • Relaxation of pelvic ligaments
  • May also affect aspects of fetal development

Question 7

Progesterone

Answer 7

• Secreted in small quantities early by corpus luteum
• Secreted in large quantities by placenta
• Functions:
  
  • Causes decidual cells to develop into the endometrium
  • Decreases contractility of pregnant uterus
  • Increases secretions of fallopian tubes and uterus
  • May work with estrogen to prepare breasts for lactation

Question 8

Human Chorionic Somatomammotropin

Answer 8

• Secreted by placenta beginning in 5^th week of pregnancy
• Causes decreased insulin sensitivity and decreased utilization of glucose by mother

Question 9

Explain the 4 theories as to why the mother’s immune system does not recognize the fetus as a foreign tissue

Answer 9

1. Lack of expression of major histocompatibility antigens by syncytiotrophoblast and cytotrophoblast (placental components)
2. Paralysis of mother’s immune system during pregnancy
3. Decidual immune barrier
4. Inactivation of mother’s immune system components (ex: T cells) by molecules formed on fetal placental surface

Question 10

Fetal Alcohol Syndrome

Answer 10

• Caused by maternal consumption of alcohol during pregnancy (b/c the placenta is permeable to alcohol)
• Infants are born addicted to heroin or crack cocaine
• Leads to a constellation of abnormalities mainly brain defects—IQ may be the same but will show deficits in recognition of the consequences of actions or planning

Question 11

Erythroblastosis Fetalis

Answer 11

Rh disease

• Maternal antibodies cause hemolysis of the Rh-positive fetal erythrocytes, Rh-positive fetuses are attacked by the maternal anti-Rh antibodies
• Occurs when fetal erythrocytes are Rh positive and the mother is Rh negative, so the presence of fetal erythrocytes in maternal circulation stimulates the formation of anti-Rh antibody by the maternal immune system

Question 12

Immune Hydrops Fetalis

Answer 12

• When the bilirubin released from the lysed RBCs cause water accumulation in the fetus with accompanying jaundice and brain damage
• Caused from severe Erythroblastosis Fetalis
• Caused by blood group incompatibility between mother and fetus
• Fetal RBCs reach the maternal blood stream during last trimester or during childbirth itself by crossing placenta

Question 13

Placenta Previa

Answer 13

• If the embryo is implanted close to the cervix, the placenta forms a partial covering over the cervical canal
• Results in hemorrhage during late pregnancy and will cause death of fetus and mother b/c of placental detachment after the hemorrhage

Question 14

Hyatidiform Mole

Answer 14

• Chorionic villi on the placenta that swell, giving them the appearance of grapes (chorionic villi are attached to the placenta to provide maximal contact with maternal blood, their genetic make-up is the same as the fetus)
• Embryo is either absent or not viable
• Result of paternal imprinting, chromosomes are 46/YY, two sperm fertilize one egg

Question 15

Teratology

Answer 15

the study of abnormal development

Question 16

Teratogen

Answer 16

agents that produce birth defects

Question 17

Malformations

Answer 17

Primary errors of morphogenesis, usually multifactorial, involving a number of etiological (causing disease) agents including genetic and environmental factors

Question 18

Disruptions

Answer 18

Disturbances in otherwise normal morphogenetic processes, Ex: amniotic bands (involves the umbilical cord and limbs of the fetus, constriction rings)

Question 19

Deformations

Answer 19

Disturbances in otherwise normal morphogenetic processes, typically caused by abnormal biomechanical forces such as uterine constraints, Ex: clubfoot

Question 20

Dysplasia

Answer 20

An abnormality of a tissue due to an abnormal intrinsic developmental process

Ex: ectodermal dysplasia

Question 21

Sequences

Answer 21

Series/cascade of events triggered by one initiating factor

Ex: oligohydramnios (decreased amniotic fluid) which leads to a variety of events, including fetal compression and other problems stemming from the fetal compression

Question 22

Syndromes

Answer 22

Constellation of congenital anomalies that are thought to be pathologically related but cannot be explained on the basis of a single local initial event

Often caused by a single event like a viral infection

Question 23

Association

Answer 23

A group of anomalies seen in more than one individual that can’t yet be attributed to a definitive cause

Question 24

Critical Period

Answer 24

A certain period during development when embryos are more susceptible to agents or factors causing abnormal development than other times

Question 25

List examples and give percentages of the three categories of causes of congenital anomalies

Answer 25

Genetic (10%)- gene mutations, chromosome rearrangements

Environmental (7%)- infections, radiation, drugs/chemicals, maternal diabetes

Multifactorial (25%)- prematurity and growth restrictions

Question 26

Gene mutations

Answer 26

• Include inborn errors of metabolism, which are rare
• Are inherited most commonly as autosomal recessive or X-linked diseases—a few are inherited as dominant traits
• Often affect enzymes and biochemical pathways
• Examples: phenylketonuria, galactosemia, cystic fibrosis

Question 27

Chromosome rearrangements

Answer 27

deletions, duplications, inversions, translocations

Question 28

Changes in chromosome number

Answer 28

Euploidy: addition of a complete set of chromosomes in addition to the diploid (2N) stage

Aneuploidy: change in chromosome number beyond the 2N stage

Question 29

Give examples of infectious agents that can result in birth abnormalities

Answer 29

• Viruses: Rubella, Cytomegalic inclusion, Herpes simplex, Varicella-zoster, Influenza, Mumps
• Bacterial
• Protozoans

Question 30

Describe the effects of thalidomide, alcohol, retinoic acid, and folic acid on birth abnormalities

Answer 30

Thalidomide: causes limb defects, ear defects, cardiovascular anomalies, Previously used to prevent uterine contractions too early so the baby isn’t born premature

Alcohol: causes growth and mental retardation, microcephaly, various malformations of face and trunk

Retinoic acid: wavefront mechanism in somitogenesis

Folic acid: deficiency causes anencephaly, prevents neural tube defects

Question 31

Describe the effects of radiation and maternal diabetes on birth abnormalities

Answer 31

Radiation can produce breaks in DNA causing mutations, and most importantly effects the development of CNS

Maternal diabetes is associated with high birth weights and stillbirths

Question 32

Neonatal Respiratory Distress Syndrome

Answer 32

Related to immaturity of the lungs in infants born prematurely, characterized by labored breathing

Incidence is inversely proportional to gestational age

​Lack of pulmonary surfactant

• Surfactant spreads over the surface of alveoli to reduce surface tension and facilitate alveoli expansion during breathing
• RDS is related to insufficiencies in the formation of surfactant by type II alveolar cells

Question 33

Eclampsia

Answer 33

Extremely high blood pressure

Proteinuria

Weight gain

Edema

Question 34

List the major risk factors of prematurity

Answer 34

• Preterm premature rupture of placental membranes
• Intrauterine infections
• Uterine, cervical, and placental structural abnormalities
• Multiple gestation

Question 35

What is the second most common cause of neonatal mortality?

Answer 35

prematurity and fetal growth constrictions