Fetal development

Question 1

Discuss the stages of fertilisation (8 stages)

Answer 1

1. Sperm meets the oocyte most commonly in the ampulla of the fallopian tube
2. The sprem is attracted to the oocyte by progesterone secreted by the cumulus cells of the oocyte
3. The sperm undergoes capacitation whereby the glycoprotien coat around the acrosomal region is removed
4. The sperm binds to the corona radiata
5. The sperm binds to ZP3 glucoprotient in the zona pellicida which triggers the acrosomal reaction
6. Enzymes are released allowing sperm penetration into the zona pellicuida
7. Once the sperm binds to the cortical granules within the egg cytoplasm enzymes are released resulting in cross linking of protiens to stop further penetration.
8. The final product is a zygote - single cell with 46 chromosomes

Question 2

Describe the steps of embryo development from the fertilisation to implantation (7 steps)

Answer 2

Day 1 - Fertilisation
Day 2 - Cleavage - division of cells within the zona pellucida
Day 3 - Compaction - divided cells compact to make the morula (from 32 cells)
Day 4 - Differentiation to form an early blastocyst with inner and outer cell mass
Day 5 - Cavitation to create a blstocele - a late blastocyst
Day 6 - Hatching from the zona pellucida. Zona pellicida made soft by lysin secreted from the inner cell mass
Day 7 - Implantation occurs with division of the trophoblasts and invasion into the endometrium.
-Formation of syncitiotrophoblasts invade to form villi
-Formation of cytotrophoblasts

Question 3

Describe the embryological events: Inner cell mass differentiation (5 points)

Answer 3

1. Inner cell mass differentiates in week 2
2. Differentiates into epiblast, hypoblast and trophoblast layers
3. Epiblast and hypoblast surround fluid filled areas.
   -Epiblast - amniotic sac
   -Hypoblast - yolk sac
4. The trophoblasts surround these two circles of cells
5. Where the two circles of cells intersecr a bilaminar disc is formed

Question 4

Describe gastrulation of embryology
-When does this occur
-What it involves
-What the layers are mae up of
-What these layers become

Answer 4

1. Gastrulation takes place in week 3
2. Involves the formation of a trilaminar disc.
3. The trilaminar disc is made from invagination of the epiblast cells at the primative streak at day 16
4. The three layers of the trilaminar are ectoderm, mesoderm, endoderm
5. The endoderm forms the skin, brain and spinal cord, PNS
6. The Mesoderm form connective tissue - muscles, bones, kidneys, circulatory system, gonads
7. The ectoderm forms the digestive tract, and other visceral organs - liver, lungs, pancreas, bladder

Question 5

Describe neurolation
-When it happens
-How it happens (3 points)

Answer 5

1. Neurolation occurs in week 4
2. The neural plate forms from the ectoderm (day 16)
3. The neural plate folds to become a tube which forms the CNS and brain
4. The neural crests become the PNS

Question 6

Describe the neural tube defects (7 types)

Answer 6

Folding of the neural plate into the neural tube begins centrally and expands to each end (Caudal and Rostral)
1. Spinda bifida - most common
-Spina bifida occulta - Some of the vertebra have failed to fuse. aSx and covered by skin.
2. Closed spina bifida - Deficiency of at least 2 vertebral arches. Defect covered with skin.
3. Meningocoele - Sac of CSF that protrudes through, not covered by skin doesn’t contain spinal cord
4. Myelomeningocoele - Bones and spinal column do not form. Spinal cord and menigies bulge. Not covered by skin. Usually partial or complete paralysis
5. Anencephaly - faiure of the NT to close at the rostral end. Open brain and lack of skull vault.
6. Craniorachischisis - complete lack of fusion of the NT. Open brain and spinal cord
7. Encephalocele - herniation of meninges +/- brain

Question 7

Discuss the organogenesis of the fetal heart
-Timing
-Tissue origin
-How it occurs

Answer 7

1. Timing
   -Develops betwen 3-8 weeks when diffusion becomes insufficient to meet the embryo’s needs
   -By day 30 the tubes are folded and flow through them
2. Derived from splanchnic mesoderm
3. The splanchnic mesoderm folds to create two endothelial tubes which fuse to become one cardiac tube

Question 8

Discus the organogenesis for the fetal lungs
-Timing
-Tissue derived from
-How it occurs

Answer 8

1. Timing
   -Develops structure between 3-8 weeks
   -By 6 weeks have primitive lungs
2. Forms from endoderm - epithelial cells and splanchnic mesoderm for cartilage, muscles amd connective tissue
3. Process:
   -Lung buds for from ventral outpouches of the the foregut at week 4
   -These develop into bronichial buds.
   -The increasing lung tissue develops into lobes

Question 9

Describe the fetal cardiopulmonary circulation
-How the blood circulates
-Major fetal specific arteries and what they connect (3)

Answer 9

1. Blood circulation pattern
   Oxygenated blood comes from the placenta -> Umbilical vein -> Ductus venosis ->IVC -> RA->LA->LV->Aorta -> common iliac -> umbillical arteries->placenta
2. Small amount of blood goes from RA to RV to pulmonary artery then pulmonary vein
3. Major fetal specific arteries
   -Ductus arteriosis - between pulmonary trunk and aortic arch
   -Patent foramen ovale - RA to LA
   -Ductus venosus - Umbillical vein to IVC

Question 10

Describe changes to fetal circulation immediately after birth

Answer 10

1. No longer has osygen supply from mother once cord has been cut
2. Increase in baby’s BP and reduction in pulmonary pressures changes and pressure gradient and the ductus arteriosis closes under the influence of bradykinin from the lungs as they inflate
3. Pressure from the LA increases and closes the foramen ovale.
4. Fluid in the respiratory system is absorbed except for surfactant
5. The umbillical vein closes by smoth muscle contraction within a few minutes after birth and becomes fibrous in a few months

Question 11

What do the following fetal structures become
1. Umbillical vein
2. Ductus venosus
3. Ductus arteriosis
4. Umbillical arteries

Answer 11

1. Medial umbilical ligament
2. Ligamentum venosis
3. Ligamentum arteriosis
4. Superior vesical artery patent and obliterated

Question 12

Discuss the development of fetal genital organs
-Timing
-Tissue origin
-Process
-Masculization
-Feminisation

Answer 12

1. Timing
   - weeks 6-8
   - Sex deterinaton possible by week 10
2. Tissue origin - intermediate mesoderm
3. Process
   -nephrogenic cord formed cranial to caudal
   -Gonadal ridge forms centrally on the nephrogenic cord
   -Primative germ cells of the yolk sac invade the gonadal ridge to form a primative gonad (nondifferentedated) at 6 weeks
   -The nephrogenic cord forms the mesonephric (Wolfarian) and paramesonephric (mullerian) ducts
4. Masculisation
   - SRY gene on Y chromosome produces SRY protient
   -SRY protient causes gonads to become teste.
   -Testes secrete testosterone and causes wolferian duct to develop into male reproductive organs
   -Some testersterone is converted to DHT aiding in the development of external male genitalia
   -Testes secrete AMH and this causes the paramesonephric duct to degenerate.
   -The external genitalia develop from the genital tubercule, urogenital fold and labiosacral swelling
5. Feminisation
   -Female development is the default. The gonad is an ovary
   -The Wolfarian duct degernerates and the mullerian duct becomes the internal female genitalia (Uterus, tubes, upper 2/3rds of the vagina)
   -The Mullerian duct fuses with the urogenital sinus at week 9
   -The urogenital sinus grows and canalises to become the lower vagina
   -The external genitalia develop from the genital tubercule, urogenital fold and labiosacral swelling

Question 13

What factors impact fetal growth
-Maternal factors (7)
-Fetal factors (4)
-Placental factors (4)
-Uterine (1)

Answer 13

1. Maternal factors: height and weight, nutrient intake, cardiorespiratory disease, renal disease, inflammatory disease, substance use, low BSL, Hypoxia
2. Fetal factors: infection, chromosomal abnormalities, cardiac disease, osteogenesis
3. Placental factors: abruption, infection, infarction, thrombosis
4. Uterine factors: decreased utero-placetnal blood flow

Question 14

Discuss the places where oxygen/acid-base and CO2 transport can be interupted and from what: 3 groups

Answer 14

1. Maternal transport to the placenta
   -Hypotension - epidural, blood loss, supine position
   -Hypertension - decreased uterine artery blood flow from vasoconstriction
   -Uterine activity - spiral arteriole occlusion with every contraction
2. Diffusion across the placenta
   -Reduced surface area - infarction, abruption, small placenta
   -Reduced O2 availability
   -Reduced fetal affintiy for O2 - acidemia, anemia
   -Uterine contractions - too many, too long
3. Fetal transport to and from placenta
   -Uterine contractions - too many too long
   -Cord events - occulsion
   -Fetal factors - anaemia, cardiac anomalies, arrythmia, fetal blood loss

Question 15

What are the fetal mechanisms to tolerate low O2 environments of uterus (4)

Answer 15

-High cardiac output
-Draw on reserves from intervillous space
-High oxygen carring capacity - reduced with acidemia
-High haemaglobin concentration

Question 16

How is the fetal heart rate controlled
-Pace maker
-Nervous system
-Role of chemoreceptors
-Role of Baroreceptors

Answer 16

1. SA node is the pace maker. Innervated by SNS and PNS
2. Nervous systems
   -SNS - mediated by catecholamines. Increases HR, BP, CO
   -PNS - mediated by acetylcholeine. Decreases HR, BP, CO
3. Role of chemoreceptors
   -Located in carotid artery, aortic arch and brainstem
   -Sensitive to hypoxia
   -Simulates vagus nerve to decrease HR to reduce O2 requirement
4. Role of baroreceptors
   -Located in carotid artery, aortic arch, brain stem
   -Sensitive to BP
   -Hypertension results in baroreceptors stimulating vagus nerve to drop HR, CO to decrease BP
   -Hypotension causes barorecptors to withdraw vagus nerve stimulation

Question 17

Discuss normal fetal movements
-Onset
-Factors which impact them (7)
-Impact of fetal sleep

Answer 17

1. Onset from 16-20 weeks
2. Perception of FM impacted by:
   -Fetal size 15% of women with IUGR have decreased FM
   -Polyhydramnios
   -Anterior placenta
   -BMI
   -Parity
   -Smoking
   -Medications
3. Babies sleep for 20-40mins and not more than 90 mins. They don’t move in this time

Question 18

Discuss the developmental steps of the placenta following implantation (14 steps)

Answer 18

1. Day 7 the blastocyst with inner and outer cell mass implants into the endometrium
2. Implantation is into the decidua functionalis
3. The trophoblastic cells have micrvilli which loosly attach to the pinopods of the decidua functionalis
4. Stronger bonds between the blastocyst and decidua functionalis are made through integrins and selectins respectively
5. Cytokines are released from the trophoblastic cells to allow invasion by the blastocyst
6. The trophoblast then differentiates into the cytotrophoblast (single layer of cells) and the syncitiotrophoblasts (multiple cells fused together)
7. The Synicitiotrophoblasts release hydrolytic enzymes which allow for stromal breakdown of the decidua functionalis
8. Syncitiotrophoblasts produce HCG which keeps the CL making progesterone to stabalse the endometrium and avoid menstruation
9. The synictiotrophoblast forms finger like projections into the stroma. Inbetween the villi are lacunae filled with blood from maternal capillary breakdown mediated by the syncitiotrophoblasts
10. The cytotrophoblasts grow through the villi and form an outer ring. The syncitiotrophoblasts with a core of cytotrophoblasts are primary villi
11. Secondary villi are formed when extra embryonic mesoderm fills the primary villi
12. The extraembryonic mesoderm then forms blood vessles - cotyledon arteries- forming tertiary villi.
13. Over weeks 4-8 these tertiary villi branch
14. The tertiary villi are seperated into groups of 2-3 by septa from the decidua basalis called cotyledons

Question 19

What are the layers of a tertiary villi (4 layers)

Answer 19

1. Fetal blood vessles
2. chorionic tissue (from the extre embryonic mesoderm)
3. Cytotrophoblasts
4. Syncitiotrophoblasts

Question 20

What structures make up the placenta (3)

Answer 20

1. Chorionic fondosum
2. Decidua basalis
3. Intervillous spaces

Question 21

What are the functions of the placenta (3 groups)

Answer 21

1. Metabolic functions
   -Gas exchange across a diffusion gradient
   -Waste removal
   -Nutrient delivery by facillitated diffusion
   -Glucose, fatty acids, amino acids, vitamins, fe
2. Immune functions
   -Transfer of IgG for passive immunity
3. Hormonal function
   -HCG - prevents regression of CL to maintain progesterone
   -Progesterone - takes over from CL at 10-12 weeks
   -Oestrogen
   -Thyroid hormone - promotes CNS development
   -Human placental lactogen - important in insulin resistance and release of fatty acids and gluconoegensis
   -Relaxin - relxes ligaments
   -Corticotrophin releasing hormone - produces cortisol for surfactant production
   -Placenta growth hormone - important for fetal growth
   -Leptin - important for placentation, implantation

Question 22

Discuss liquor physiology
-Origins
-How it is removed
-What are normal amounts at term
-What are it’s functions (4)

Answer 22

1. Amniotic fluid origin
   -Amniotic fluid is initally secrete from the amnion
   -By weeks 10 it is largely a transuate of fetal serum from the fetal skin and umbilical cord
   -By Week 16 it is made by the kidneys and is hypertonic
2. It is removed by:
   -fetal swallowing and absorption into the fetus by the GIT
   -Fetal breathing which moves amniotic fluid into the lungs
   -Across the chorion - due to relative hypotonic nature of the fluid
3. Normal amounts at term are less than at 32 weeks when it peaks. Normal amount is about 800mL at term
4. Functions of amniotic fluid
   -Protection of the fetus from mechanical injury
   -Fetal movement and limb development
   -Prevents adhsions between fetus and amnion
   -Permits lung development

Question 23

Describe the changes to the lungs that occur with birth (7)

Answer 23

1. In utero the lungs are fluid filled. During vaginal delivery the fluid is squeezed out through chest compression
2. Through tactile, chemical and thermal stimulation the baby is prompted to gasp
3. Gasping causes negative intrathoracic pressure and oxygen is sucked into the lungs
4. The fluid in the aveolar is pushed into the circulation and lymphatics
5. Surfactant in the lungs reduces aveolar surface tension to allow this to occur
6. Increased oxygen in the pulmonary circulation reduces pulmonary vascular resistance
7. A fall in the pulmonary resistance and a rise in systemic resistance equalises the pressures across the foramen ovale and ductus arteriosis and the flow stops.

Question 24

Discuss apgar scores
-What indicators make up an apgar score (5)
-What scores suggests excellent, moderate and severly depressed conditions
-How do scores correlate with outcomes (2)

Answer 24

1. Indicators of apgar scores - 0,1, or 2 points)
   -Appearence (skin colour)
   -Pulse (>100 normal)
   -Grimace
   -Activity (muscle tone)
   -Respiration
2. Scores
   Excellent - >6
   Moderately depressed 4-6
   Severly depressed 0-3
3. OUtcome correlations
   The apgar at 1 minute is not predicitive of long term outcomes
   An APGAR less than 7 at 5 mins increases risk of CP