FETAL PHYSIOLOGICAL DEVELOPMENT

CARDIOVASCULAR SYSTEM

Fetal Circulation• Nutrients for growth and development are

delivered from the umbilical vein in the umbilical cord → placenta → fetal heart

Fetal Circulation Oxygenated blood from mother

↓ (via umbilical vein) Liver

Portal sinus Ductus venosus↓

Inferior vena cava (mixes with deoxygenated blood)

↓Right atrium

Right atrium ↓ (through Foramen ovale)

Left atrium↓

Left ventricle ↓ (through Aorta)

Heart and Brain

Deoxygenated blood from lower half of fetal body ↓Inferior vena cava

Right atrium ↓

Right ventricle

Deoxygenated blood flowing through

Superior vena cava

Right ventricle↓

Pulmonary artery ↓ (through Ductus arteriosus)

Descending aorta↓

Hypogastric arteries ↓

Umbilical arteries↓

Placenta

Fetal Circulation

Source: http://images.google.com.ph

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

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.

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

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

Changes After Birth: Closing of Shunts

Shunt 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

Within several mins after birth

3 – 7 days after birth

Ligamentum venosum

Umbilical arteries → Umbilical ligaments

Umbilical vein → Ligamentum teres

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.

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)

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

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)

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

Fetal Blood

Type Description Chains

Hemoglobin F Fetal Hgb or alkaline-resistant Hgb

2 alpha chains, 2 gamma chains

Hemoglobin A Adult Hgb. Formed starting at 32-34 wks gestation and results from methylation of gamma globin chains

2 alpha chains, 2 beta chains

Hemoglobin A2

Present in mature fetus in small amounts that increase after birth

2 alpha chains,2 delta chains

Fetal Hemoglobin

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)

Oxygen dissociation curve of fetal and maternal blood

Source: http://www.colorado.edu/intphys/Class/IPHY3430-200/image/18-12.jpg

Fetal BloodFetal 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

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

Fetal BloodImmunocompetence 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

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

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

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

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 18-20 wks

NERVOUS SYSTEM and SENSORY ORGANSGestational

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

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

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.

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

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

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)