Lecture 12: Placental Physiology and Developmental Disorders Flashcards
List functions of the placenta
Diffusion of oxygen and carbon dioxide
Diffusion of foodstuffs
Excretion of wast products
Compare the early placenta with the late placenta
Early: Thick, Permeability low, Small surface area, Total diffusion conductance is miniscule
Late: Permeability high, Large surface area, Large increase in placental diffusion
Describe the oxygen pressure gradient (near end of pregnancy) and explain why adequate oxygenation can occur with such a low pressure gradient
- 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
Describe the Bohr effect and the double Bohr effect
- 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
Human Chorionic Gonadotropin
- Secreted by the syncytial trophoblast cells into maternal fluids
- Measurable secretion 8-9 days after ovulation
- Maximal secretion during 10th- 12th week of pregnancy
- Lower levels secreted 16th through 20th 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
Estrogens
- 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
Progesterone
- 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
Human Chorionic Somatomammotropin
- Secreted by placenta beginning in 5th week of pregnancy
- Causes decreased insulin sensitivity and decreased utilization of glucose by mother
Explain the 4 theories as to why the mother’s immune system does not recognize the fetus as a foreign tissue
- Lack of expression of major histocompatibility antigens by syncytiotrophoblast and cytotrophoblast (placental components)
- Paralysis of mother’s immune system during pregnancy
- Decidual immune barrier
- Inactivation of mother’s immune system components (ex: T cells) by molecules formed on fetal placental surface
Fetal Alcohol Syndrome
- 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
Erythroblastosis Fetalis
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
Immune Hydrops Fetalis
- 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
Placenta Previa
- 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
Hyatidiform Mole
- 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
Teratology
the study of abnormal development
Teratogen
agents that produce birth defects
Malformations
Primary errors of morphogenesis, usually multifactorial, involving a number of etiological (causing disease) agents including genetic and environmental factors
Disruptions
Disturbances in otherwise normal morphogenetic processes, Ex: amniotic bands (involves the umbilical cord and limbs of the fetus, constriction rings)
Deformations
Disturbances in otherwise normal morphogenetic processes, typically caused by abnormal biomechanical forces such as uterine constraints, Ex: clubfoot
Dysplasia
An abnormality of a tissue due to an abnormal intrinsic developmental process
Ex: ectodermal dysplasia
Sequences
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
Syndromes
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
Association
A group of anomalies seen in more than one individual that can’t yet be attributed to a definitive cause
Critical Period
A certain period during development when embryos are more susceptible to agents or factors causing abnormal development than other times
List examples and give percentages of the three categories of causes of congenital anomalies
Genetic (10%)- gene mutations, chromosome rearrangements
Environmental (7%)- infections, radiation, drugs/chemicals, maternal diabetes
Multifactorial (25%)- prematurity and growth restrictions
Gene mutations
- 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
Chromosome rearrangements
deletions, duplications, inversions, translocations
Changes in chromosome number
Euploidy: addition of a complete set of chromosomes in addition to the diploid (2N) stage
Aneuploidy: change in chromosome number beyond the 2N stage
Give examples of infectious agents that can result in birth abnormalities
- Viruses: Rubella, Cytomegalic inclusion, Herpes simplex, Varicella-zoster, Influenza, Mumps
- Bacterial
- Protozoans
Describe the effects of thalidomide, alcohol, retinoic acid, and folic acid on birth abnormalities
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
Describe the effects of radiation and maternal diabetes on birth abnormalities
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
Neonatal Respiratory Distress Syndrome
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
Eclampsia
Extremely high blood pressure
Proteinuria
Weight gain
Edema
List the major risk factors of prematurity
- Preterm premature rupture of placental membranes
- Intrauterine infections
- Uterine, cervical, and placental structural abnormalities
- Multiple gestation
What is the second most common cause of neonatal mortality?
prematurity and fetal growth constrictions
