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LECTURE OUTLINEFetal stages

Fetal circulationFetal blood

Nervous system

Gastro-intestinal systemUrinary system

Pulmonary systemEndocrine glandsFetal gender

FETAL STAGES

A fetus is a developing mammal after the embryonic stage and before birth.

In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.

At the start of the fetal stage, the fetus is typically about 30 mm in length from crown to rump, and weighs about 8 grams.

The head makes up nearly half of the fetus’ size.

Breathing-like movement of the fetus is necessary for stimulation of lung development, rather than for obtaining oxygen.

The heart, hands, feet, brain and other organs are present, but are only at the beginning of development and have minimal operation.

Fetuses are not capable of feeling pain at the beginning of the fetal stage, and may not be able to feel pain until the third trimester.

At this point in development, uncontrolled movements and twitches occur as muscles, the brain and pathways begin to develop.

FETAL STAGES Week 16 to 25

A primiparous woman typically feels fetal movements at about 21 weeks, whereas a multiparous woman will typically feel movements by 20 weeks.

By the end of the fifth month, the fetus is about 20 cm. Week 26 to 40

The amount of body fat rapidly increases. Lungs are not fully mature. Thalamic brain connections, which mediate sensory input, form.Bones are fully developed, but are still soft and pliable.

Iron, calcium, and phosphorus become more abundant.

Fingernails reach the end of the fingertips. The lanugo begins to disappear, until it is gone except on the upper arms and shoulders.

Small breast buds are present on both sexes. Head hair becomes coarse and thicker.

Birth ccurs around the 40th week, but the fetus is considered full-term between wks 37 and 40- it is sufficiently developed for life outside.

It may be 48-53 cm in length.

Control of movement is limited at birth, and purposeful voluntary movements develop all the way until puberty.

Variation in growth

There is much variation in the growth of the fetus. factors affecting fetal growth can be:

Maternal factors include maternal weight, body mass index, nutritional state, emotional stress, toxin exposure and uterine blood flow.

Placental factors include size, microstructure, umbilical blood flow, transporters and binding proteins, nutrient utilization and nutrient production.

Fetal factors include the fetus genome, nutrient production,

and hormone output. Female fetuses tend to weigh less than males at term.

Low birth weight increases risk for perinatal mortality, asphyxia, hypothermia, and other abnormalities, and long-term health problems.

Viability refers to a point in fetal development at which the fetus may survive outside the womb.

The lower limit of viability is approximately five months gestational age, and usually later.

Variation in growth

There is no sharp limit of development at which a fetus automatically becomes viable.

According to data years 2003-2005, 20-35 % of babies born at 23 weeks of gestation survive

50 to 70 % of babies born at 24-25 wks, and more than 90% born at 26-27 wks, survive.

It is rare for a baby weighing less than 500 gm to survive.

When such babies are born, the main causes of perinatal mortality is that the respiratory system and the CNS are not completely differentiated.

If given expert postnatal care, some fetuses weighing less than 500 gm may survive, and are referred to as extremely low birth weight or immature infants.

Preterm birth is the most common cause of perinatal mortality, causing almost 30% of neonatal deaths.

Function of amniotic fluidCushion fetus

Protects from traumaMaintain temperature

Minimal nutritive function

Allows for unobstructed fetal growth development of tissuesProtects umbilical cord

Allows for normal development of the respiratory tract, gastrointestinal tract, and musculoskeletal system

Contains epidermal growth factor and epidermal-like growth factorsProvides a bacteriostatic environment

Others

Postnatal development: Circulatory SystemThe circulatory system of fetus works differently from that of born humans; the

lungs are not in use: the fetus obtains O2 and nutrients from the mother through the placenta and the umbilical cord.

Blood from the placenta is carried to the fetus by the umbilical vein. About half of this enters the fetal ductus venosus and is carried to the inferior vena cava,

while the other half enters the liver proper from the inferior border of the liver. The branch of the umbilical vein that supplies the right lobe of the liver first joins with the portal vein. The blood then moves to the right atrium of the heart.

There is an opening between the RA and LA, Foramen ovale, and most of the blood flows from the RA into the LA, thus bypassing pulmonary circulation.

The majority of blood flow is into the LV from where it is pumped through the aorta into the body.

Some of the blood moves from the aorta through the internal iliac arteries to the umbilical arteries, and re-enters the placenta, where CO2 and other waste products from the fetus are taken up and enter the mother’s circulation.

Some of the blood from the RA does not enter the LA, but enters the RV and is pumped into the pulmonary artery.

There is a special connection between the pulmonary artery and the aorta, called the ductus arteriosus, which directs most of this blood away from the lungs.

Fetal circulation

Postnatal development: Circulatory System

When the infant takes first breath after birth, the system changes suddenly. The pulmonary resistance is dramatically reduced.

More blood moves from the RA to the RV and into the pulmonary arteries, and less flows through the foramen ovale to the LA.

The blood from the lungs travels through the pulmonary veins to the LA, increasing the pressure there. The decreased right atrial pressure and the increased left atrial pressure pushes the septum primum against the septum secundum, closing the foramen ovale, which now becomes the fossa ovalis.

This completes the separation of the circulatory system into two halves, the left and the right.

The ductus arteriosus normally closes off within 1-2 days of birth, leaving behind the ligamentum arteriosum.

The umbilical vein and the ductus venosus closes off within 2-5 days after birth, leaving behind the ligamentum teres and the ligamentum venosus of the liver respectively.

Fetal hemoglobin enhances the fetus’ ability to draw O2 from the placenta. Its dissociation curve to O2 is shifted to the left, meaning that it will take up O2 at a lower concentration than adult hemoglobin will.

This enables fetal hemoglobin to absorb O2 from adult hemoglobin in the placenta, which has a lower pO2 than at the lungs.

Fetal circulationFirst organ system to be functional

Gas exchange occurs in the placenta

Ventricles work in parallel and not on seriesPreferential flow of blood

Flow of blood facilitated by shunts:

Ductus arteriosus –diverts blood away from PA to aortaForamen ovale –opening between left and right atrium

Ductus venosus –diverts blood coming from the placenta away from liver

Foramen ovale

Ductus arteriosus

Ductus venosus Umbilical arteries ligamentsUmbilical vein

Closes shortly after birth Fuses completely in first year

Closes soon after birth Ligamentum arteriosum

Ligamentum venosum Medial umbilical

Ligamentum teres

SEQUENCE OF EVENTS AT BIRTH

A

Placental circulation cut off. Umbilical Vein Clamped

Umbilical Vein Collapses

Sudden Pressure Drop Right side of the heart

Septum secundum slaps on septum primum

Closing the foramen ovale

100mls blood gushes through ductus venosus Into the right atrium

B

Severe Asphyxia

First Gasp of Life

Lungs expand to 50mmHg Pressure

Suction Pressure

Pulmonary Vasculature Resistance drops to less than 20%

All right side blood enters Right ventricle and forces pulmonary artery flow

Blood Sucked from Right Atrium through pulmonary artery flow

Increased left Atrial Pressure

RESULTS

Blood now returns to right atrium, flows through each valve to the lungs and the left vetricle and its pumped out to the

body from the left ventricle “in series” circulation.

The pressure changes cause D.A to collapse and close in 24 -48Hrs.

Fetal oxygenation

• Fetal hemoglobin: increased O2 affinity • Decreased fetal oxygen consumption:

– No need for thermoregulation

-Reduced many physiologic functions -Differential blood flow

HgF has increased O2 binding capacity

HgA binds 2,3 DPG more avidly then Hgb F

Increased temperatures and decreased pH lowers this binding capacity

Fetal oxygenation

A right shift indicates

decreased O2 affinity.

The P50 is higher for a right shifted curve.

A right shift can be caused by an increase in:

temperature pCO2

red cell 2,3 DPG level. And decrease [H+]

Fetal oxygenation

Progesterone increases sensitivity to CO2 i.e. the respiratory center (medulla oblongata) can’t tolerate the usual amount of

CO2 in the blood.

This accounts for the feeling of shortness of breath, dyspnea, or heightened awareness of the need to breathe reported by many pregnant women. The pregnant woman is

actually forced to hyperventilate, and “blow off” more CO2 than she normally would.

As a result, the removal of CO2 from the fetus’s bloodstream is facilitated!

In a blood gas analysis, the normal nonpregnant woman would be expected to have a pCO2 of 35-45 mmHg

Whereas the normal pregnant woman would be expected to have a pCO2 of 27-32 mmHg.

Fetal blood

Hemopoiesis

• Yolk sac: early embryo • Liver

• Bone marrow

initially nucleated RBCs Hb 12g/dl at midpregnancy Hb 18 g/dl at term

Short life span: high reticulocyte count

Fetal Blood:continued

• Erythropoiesis: fetal erythropoietin

• Fetal blood flow: fetoplacental blood volume 125 mL/ kg of fetus.

• Fetal Hemoglobin: Hb F falls during latter weeks of pregnancy. At term ¾ Hb F

Hb F bind more O2 at any given O2 tension and identical pH

Hb A binds 2,3-DPG more avidly than Hb F

Variety of fetal hemoglobinsGenes turned on and offMethylation turns genes off

Timing of production corresponds to change in production site

αchains –chromosome 16Final adult form –6 weeks’

βchains –chromosome 11Gamma and delta continue to be formed

Glucocorticoids mediate the irreversible switch from fetal to adult HGB

Fetal Blood: continued

• Fetal coagulation factors: decreased platelets: normal

• Fetal plasma proteins

• Fetal immunocompetence: IgG

Lymphocytes,deficient

Nervous system

• At 10 weeks: Local stimuli evoke response • Swallowing:10 w

• Respiration :14-16 w

• Mature taste buds receptors;12 w • Ability to suck: 24 w

• Integration of nervous and muscular function increase rapidly in third trimester

• Hears sound:24-26 w

• Eye sensitive to light: 28 w

Spina bifida (“split spine”) is a developmental congenital disorder caused by the incomplete closing of the embryonic neural tube.

Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open.

If the opening is large enough, this allows a portion of the spinal cord to protrude through the opening in the bones. There may or may not be a fluid-filled sac surrounding the spinal cord.

Gastrointestinal systemSwallowing: 10-12 w

Peristalsis and transport of glucose: 10-12 wAmniotic fluid regulated by swallowing

Hydrochloric acid and digestive enzymes: stomach and small intestine, early fetus.

Movement of fluid in GI may enhance growth and development of GI tract

Meconium : desquamated fetal cells, lanugo, scalp hair, vernix, debris and secretions.

passage: normal

in response to hypoxia (AVP)Liver : enzymes increase with GA

Pancreas : insulin in fetal plasma, 12 w

G I system: continued

Research in several species has established the quantitative importance of glucose as a fetal and placental nutrient.

Measurements of arteriovenous concentration differences across the uterine and umbilical circulations have shown that the placenta takes up glucose from maternal blood and releases it into the umbilical circulation .

The quantity of glucose delivered into the umbilical circulation is less than the quantity taken up from the uterine circulation;

this reflects the fact that the placenta uses glucose as a metabolic fuel

glucose is the main substrate o f cerebral oxidative metabolism in prenatal a s well as postnatal l i f e .

fetal heart utilizes mainly glucose and lactate . This is in sharp contrast to the adult heart for which FA and AA are the most important metabolic fuels.

Gastrointestinal system

Maternal nutrition plays a critical role in fetal growth and development.

Although considerable effort has been directed towards defining nutrient requirements of animals over the past 30 y, suboptimal nutrition during gestation remains a significant problem for many animal species.

Despite advanced prenatal care for mothers and fetuses, 5% of human infants born in the U.S. suffer from intrauterine growth retardation

Over the past decade, compelling epidemiological studies have linked IUGR with the etiology of many chronic diseases in adult humans and animals.

These intriguing findings have prompted extensive animal studies to identify the biochemical basis for nutritional programming of fetal development and its long-term health consequences.

Urinary systemPronephros, mesonephros then metanephros.Pro and mesonephros degenerate by 11-12 wFailure to form or regress result in anomalies

Between 9-12 w, ureteric bud and nephrogenic blastoma interact to produce metanephros

14 w, loop of Henle functional

Kidneys start producing urine at 12 w

Kidneys :Not essential for survival in utero,

Impotant in contol in composition and volume of amniotic fluid

Pulmonary systemPsudoglandular stage: 5-17 w

Canalicular stage: 16-25 w

Terminal sac stage: type ii cells begin to produce surfactant

At birth only 15% of adult alveoli are present,lungs continue to grow up to 8 years

The surfactant (abbreviation for surface active agent) consists ofglycerophospholipids, specific proteins, neutral fats and cholesterol.

It covers the alveolar surface and reduces the surface tension so that, following birth, the alveoli do not collapse during the expiration.

Composition:90% lipids, 10% proteins

Glycerophosphlipids: 80% phosphatidylcholine (lecithins):

At birth,with first breath, an air to tissue interface is produced in the alveolus. Surfactant uncoils from lammeller bodies and then spreads to line alveolus to prevent collapse during expiration

Endocrine glands

• Pituitary : ACTH,GH,TSH, and LH 13 w • Posterior pituitary: 10-12 w

• Thyroid : 10-12 w

• Adrenal glands : fetal zone disappears after birth

Fetal gender

• Chromosomal sex • Gonadal sex

• phenotypic sex presence of Y crm

testis determining factor (TDF) dose dependent sex reversal (DDs)

SUMMARY OF FETAL ADAPTATIONS AND ADJUSTMENTS AT

BIRTH 1. RESPIRATORY ADAPTATIONS

Site of oxygenation changes from placenta/umbilical vein.

2. CIRCULATORY ADJUSTMENTS

a) Reversal of oxygenated blood from IVC to Right Atrium to PVR to Venticle to Aorta

b) Collapse of umbilical vein reduction of portal vein (shunt) drop in right atrial Pressure

c) Suction of blood into pulmonary vascular system.

d) Pulmonary Artery blood flow

e) Pulmonary veins blood flow into left ventricle.

f) CLOSURE OF FARAMEN CLOSURE OF

OVALE DUCTUS ARTERIOSUS

g) Complete reversal of PARALLEL FLOW (Shunt) to IN SERIES FLOW Right heart to left Heart.

3. HAEMOGLOBIN CHANGE

From HBF to HbA

Over two months

Change in O2/Hb dissociation curve

4. TEMPERATURE ADJUSTMENT

370C to 220C (ambient)

effect on enzymes, glucose utilization, etc.

5. OTHERS

Swallowing

Excretion

Physical Environment

Congenital anomalies are anomalies that are acquired before birth.

Patent ductus arteriosus, where the ductus does not properly close, drugs that inhibit prostaglandin synthesis can be used to encourage its closure, so that surgery can be avoided.

Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain. With age, the PDA may lead to congestive heart failure if left uncorrected.

A developing fetus is highly susceptible to anomalies in its growth and metabolism, increasing the risk of birth defects. Diet is especially important in the early stages of development. Studies show that supplementation of the woman’s diet with folic acid reduces the risk of spina bifida and other neural tube defects.

Another dietary concern is whether the woman eats breakfast. Skipping breakfast could lead to extended periods of lower than normal nutrients in the woman’s blood, leading to a higher risk of prematurity, or other birth defects in the fetus.

During this time alcohol consumption may increase the risk of the development of Fetal alcohol syndrome, a condition leading to mental retardation in some infants.

Smoking during pregnancy may also lead to reduced birth weight. Low birth weight is defined as 2500 g. Such infants tend to have a higher risk of secondary medical problems.

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