1. FETAL PHYSIOLOGICAL DEVELOPMENT

2. CARDIOVASCULAR SYSTEM
Fetal Circulation
Nutrients for growth and development are delivered from the umbilical vein in the umbilical cord → placenta → fetal heart

3. Fetal Circulation Oxygenated blood from mother ↓ (via umbilical vein)
Liver
Portal sinus Ductus venosus ↓
Inferior vena cava (mixes with
deoxygenated blood)
Right atrium

4. ↓ (through Foramen ovale)
Right atrium
↓ (through Foramen ovale)
Left atrium ↓
Left ventricle
↓ (through Aorta)
Heart and Brain

5. Deoxygenated blood flowing through Superior vena cava
from lower half of
fetal body ↓
Inferior vena cava
Right atrium
Right ventricle
Deoxygenated blood flowing through Superior vena cava

6. ↓ (through Ductus arteriosus)
Right ventricle ↓
Pulmonary artery
↓ (through Ductus arteriosus)
Descending aorta
Hypogastric arteries
Umbilical arteries
Placenta

7. Fetal Circulation
Source:

8. Differences in Fetal and Adult Circulation
1st difference:
Presence of shunts which allow oxygenated blood to bypass the right ventricle and pulmonary circulation, flow directly to the left ventricle, and for the aorta to supply the heart and brain
3 shunts:
- Ductus venosus
- Foramen ovale
- Ductus arteriosus

9. Differences in Fetal and Adult Circulation
2nd difference:
Ventricles of the fetal heart work in parallel compared to the adult heart which works in sequence.

10. Differences in Fetal and Adult Circulation
Fetal cardiac output per unit weight is 3 times higher than that of an adult at rest.
This compensated for low O2 content of fetal blood.
Is accomplished by ↑ heart rate and ↓ peripheral resistance

11. Changes After Birth
Clamped cord + fetal lung expansion = constricting and collapsing of umbilical vessels, ductus arteriosus, foramen ovale, ductus venosus
Fetal circulation changes to that of an adult

12. Changes After Birth: Closing of Shunts
Functional closure
Anatomical closure
Remnant
Ductus arteriosus
10 – 96 hrs after birth
2 – 3 wks after birth
Ligamentum arteriosum
Formamen ovale
Within several mins after birth
One year after birth
Fossa ovalis
Ductus venosus
3 – 7 days after birth
Ligamentum venosum
Umbilical arteries → Umbilical ligaments
Umbilical vein → Ligamentum teres

13. Changes After Birth Maintenance of ductus arteriosus depends on:
- difference in blood pressure bet. Pulmonary artery and aorta
- difference in O2 tension of blood passing through ductus. ↑ p O2 = stops flow. Mediated through prostaglandins.

14. Fetal Blood Hematopoiesis
First seen in the yolk sac during embryonic period (mesoblastic period)
Liver takes over up to bear term (hepatic period)
Bone marrow: starts hematopoietic function at around 4 months fetal age; major site of blood formation in adults (myeloid period)

15. Fetal Blood Hematopoiesis
Erythrocytes progress from nulceated to non-nucleated
Blood vol. and Hgb concentration increase progressively
Midpregnancy: Hgb 15 gms/dl
Term: 18 gms/dl

16. Fetal Blood Hematopoiesis
Fetal erythrocytes: 2/3 that of adult’s (due to large volume and more easily deformable)
During states of fetal anemia: fetal liver synthesizes erythropoietin and excretes it into the amniotic fluid. (for erythropoiesis in utero)

17. Fetal Blood Fetal Blood Volume
Average volume of 80 ml/kg body wt. right after cord clamping in normal term infants
Placenta contains 45 ml/kg body weight
Fetoplacental blood volume at term is approx. 125 ml/kg of fetus

18. Fetal Blood Fetal Hemoglobin Type Description Chains Hemoglobin F
Fetal Hgb or alkaline-resistant Hgb
2 alpha chains,
2 gamma chains
Hemoglobin A
Adult Hgb. Formed starting at wks gestation and results from methylation of gamma globin chains
2 beta chains
Hemoglobin A2
Present in mature fetus in small amounts that increase after birth
2 delta chains

19. Fetal Blood Fetal Hemoglobin
Fetal erythrocytes that contain mostly Hgb F bind more O2 than Hgb A erythrocytes
Hgb A binds more 2-3 BPG more tightly than Hgb F (this lowers affinity of Hgb for O2)
Increased O2 affinity of fetal erythrocytes results from lower concentartion of 2-3 BPG in the fetus
Affinity of fetal blood for O2 decreases at higher temp. (maternal hyperthermia)

20. Oxygen dissociation curve of fetal and maternal blood
Source:

21. Fetal Blood Fetal Coagulation Factors
Contains lowers levels of coagulation factors II, VI, IX, X, XI, XII, XIII and fibrinogen (vit. K dependent factors)
Routine prophylaxis of vit. K injections to prevent hemorrhagic disease of the newborn
Platelet count is normal
Thrombin time prolonged
Factor XIII (fibrin stabilizing factor) & plasminogen lower than adult
Low level of factor VIII → hemophilia in male infants

22. Fetal Blood Fetal Plasma Proteins and Blood Viscosity
Mean total plasma protein, Plasma albumin concentration, and Blood viscosity: similar in maternal & fetal blood
Increased viscosity in fetal blood: due to higher Hct. Is offset by lower levels of fibrinogen and IgM, and by more deformable erythrocytes

23. Fetal Blood Immunocompetence of Fetus
IgG from mother begins at around 16 wks and is most pronounce during last 4 wks or pregnancy
Newborns produce IgG and adult values are reached at 3 years old
IgM produced by fetus in response to congenital infections (Rubella, CMV, Toxoplasmosis)
Adult levels of IgM attained by 9 mos old

24. Fetal Blood
B lymphocytes appear in liver by 9 wks gestation, and seen in the blood and spleen by 12 wks gestation
T lymphocytes produced by thymus at 14 wks
Monocytes of newborns able to process and present antigen when tested w/ maternal antigen-specific T-cells

25. Fetal Blood Ontogeny of the Immune Response
Hemolytic disease of the newborn: maternal antibodies to fetal erythrocyte antigen cross the placenta to destroy fetal erythrocytes
Fetus is immunologically competent at 13 wks AOG
Synthesis of complement in late 1st trimester. At term, complement levels are ½ of adults

26. Fetal Blood Ontogeny of the Immune Response
Newborn responds poorly to immunization (due to deficient response of newborn B cells or lack of T cells)
Only IgA from colostrum may protect against enteric infections
IgM predominantly produced in response to antigenic stimulation. Identification may help diagnose intrauterine infections

27. NERVOUS SYSTEM and SENSORY ORGANS
Sufficient development of synaptic functions are signified by flexion of fetal neck & trunk
If fetus is removed from the uterus during the 10th wk, spontaneous movements may be observed although movements in utero aren’t felt by the mother until wks

28. NERVOUS SYSTEM and SENSORY ORGANS
Gestational age
Fetal development
10 wks
Squinting, opening of mouth, incomplete finger closure, plantar flexion of toes, swallowing and respiration
12 wks
Taste buds evident histologically
16 wks
Complete finger closure
24 – 26 wks
Ability to suck, hears some sounds
28 wks
Eyes sensitive to light, responsive to variations in taste of ingested substances

29. DIGESTIVE SYSTEM
11 wks gestation → peristalsis in small intestine, transporting glucose actively
16 wks gestation → able to swallow amniotic fluid, absorb much water from it, and propel unabsorbed matter to lowe colon
Hydrochloric acid & other digestive enzymes present in very small amounts

30. DIGESTIVE SYSTEM
Term fetuses can swallow 450 ml amniotic fluid in 24 hours
This regulates amniotic fluid volume:
- inhibition of swallowing (esophageal atresia) = Polyhydramnios
Amniotic fluid contributes little to caloric requirements of fetus, but contributes essential nutrients: 0.8 gms of soluble protein is ingested daily by the fetus from amniotic fluids. Half is alubumin.

31. DIGESTIVE SYSTEM Meconium passed after birth
Dark greenish black color of meconium caused by bile pigments (esp. biliverdin)
Meconium passage during labor due to hypoxia (stimulates smooth muscle of colon to contract)
Small bowel obstruction may lead to vomiting in utero
Fetuses with congenital chloride diarrhea may have diarrhea in utero. Vomiting and diarrhea in utero may lead to polyhydramnios and preterm delivery

32. DIGESTIVE SYSTEM Liver and Pancreas
Fetal liver enzymes reduced in amount compared to adult
Fetal liver has limited capacity to convert free bilirubin to conjugated bilirubin
Fetus produces more bilirubin due to shorter life span of fetal erythrocytes. Small fraction is conjugated and excreted and oxidized to biliverdin
Much bilirubin is transferred to the placenta and to the maternal liver for conjugation and excretion

33. DIGESTIVE SYSTEM Fetal pancreas responds to hyperglycemia by ↑ insulin
Insulin containing granules identified in fetal pancreas at 9-10 wks. Insulin in fetal plasma detectable at 12 wks.
Insulin levels: ↑ in newborns of diabetic mothers and LGAs (large for gestational age); ↓in infants who are SGA (small for gestational age)