FETAL MORPHOLOGICAL AND PHYSIOLOGICAL DEVELOPMENT

Enrique V. Labios, MD, FPOGS, FPSUOG (12-09-2013)

Obstetrics and Gynecology

DETERMINATION OF GESTATIONAL AGE MORPHOLOGICAL GROWTH

 Time elapsed since the first day of LNMP  Ovum
 Method of fetal aging is useful for those who have  Zygote
regular cycles of menstruation  Blastocyst
 The first day of the LNMP precedes conception  Embryo
 2 weeks before ovulation and fertilization  Fetus
and nearly three weeks before implantation
of the blastocyst FETAL PERIOD
 The standard: Calculate gestational age as  Begin by 8 weeks after fertilization
menstrual age  10 weeks onward by menstrual age
 Average duration is 280 days (40 weeks)  End of embryonic period
 Corresponds to 91/3 calendar months  Beginning of fetal period
 Corresponds to 10 lunar months  Embryo-fetus = 4 cm long
 1 lunar month = 28 days  Major portion of lung development is yet to occur
 Delivering a baby normally can start
from 37 weeks and extend duration up
*The end of the embryonic period and the beginning of the
to 2 weeks (42 weeks) fetal period is arbitrarily designated by most embryologists to
 Calculate gestational age begin 8 weeks after fertilization or 10 weeks after onset of last
 Example: Oct 1, 2013 menses. At this time, the embryo fetus is nearly 4 cm long.
 Last menstrual period (Day 1) = Oct 1, 2013
 Oct 1 to Dec 9 =? days
 ? days = 10 weeks  Fetal period - Consists of growth and maturation
of structures that were formed during the
embryonic period
*If you suspect a pregnancy, First thing you will do is conduct
a pregnancy test. That is 3-7 days after your missed period.
By using a pregnancy test, 97% of cases will turn positive.
*Customarily we calculate GA as menstrual age. Example: If
the first day of LMP is Oct. 1, 2012, menstrual age today is 10
weeks.

DETERMINATION OF EDD (40 WEEKS)

 Calculate Expected Date of Delivery (EDD)
 Formula (Naegele’s Rule): First day of LMP plus 7
days and minus 3 months
 Example: Last menstrual period (Day 1) = Oct 1, *Actual
2013
 10 / 01 / 2013
 -3 +7
 7 / 08 / 2014
 July 8, 2014 (EDD: 40 weeks)

TRIMESTERS OF PREGNANCY
 The period of gestation can also be divided into
three units of three calendar months (13 weeks)
each
 These three trimesters have become important
obstetrical milestones. *2D scan of the fetus, approximately 10 weeks
 Up until 13 weeks and 6 days = 1st trimester
(inclusive of embryonic period)
 14 weeks – 27 weeks = 2nd trimester
(maturation of the fetus)
 28 weeks – 42 weeks = 3rd trimester
 The period of gestation can also be divided
into three units of three calendar months (13
weeks) each
 These three trimesters have become
important obstetrical milestones.
*3D rendering

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 CRITERIA FOR ESTIMATING AGE DURING THE FETAL PERIOD

MENSTRUAL CRL (mm) WEIGHT (g) MAIN EXTERNAL CHARACTERISTICS

External genitalia still not distinguishable as male or female. Intestines are in the
11 50 8
umbilical cord.
14 87 45 Sex (Genitalia) distinguishable externally. Well-defined neck.
16 120 110 Head erect. Lower limbs well developed.
18 140 200 Ears stand out from head.
20 160 320 Vernix caseosa present. Early toenail development.
24 210 630 Skin wrinkled and red. eyebrows and eyelashes are usually recognizable
28 250 1000 Eyes partially open. Eyelashes present.
34 300 2100 Fingernails reach fingertips. Skin pink and smooth.
38 340 2900 Body usually plump. Lanugo hairs almost absent. Toenails reach toe tips.
Prominent chest; breasts protrude. Testes in scrotum or palpable in inguinal
40 360 3400
canals. Fingernails extend beyond fingertips.
*Crown-Rump Length (head to butt area)
*These measurements are average and so may not apply to specific cases; dimensional variations increase with age.
*These weights refer to fetuses that have been fixed for about 2 weeks in 10-percent formalin.
*Fresh specimens usually weigh approximately 5 percent less.
*MEMORIZE THIS TABLE ESP. THE EXTERNAL CHARACTERISTICS

FETAL PERIOD

GESTATIONAL AGE LENGTH CHARACTERISTICS

12 weeks 6 to 7 (+) Centers of ossification; fingers and toes; skin and nails; movement; genitalia
16 weeks 12 cm Weight = 110 G
20 weeks 16 cm Weight = 300 G; skin less transparent; lanugo covers the entire body; scalp hair
Weight = 630 G; skin is wrinkled; fat deposition begins; bronchi, bronchioles,
24 weeks 21 cm
alveolar duct development is nearly completed
Weight = 1100 G; skin is red covered with vernix caseosa; pupillary membrane
28 weeks 25 cm
has just disappeared from the eyes
32 weeks 28 cm Weight = 1800 G; skin is still red and wrinkled
36 weeks 32 cm Weight = 2500 G; skin wrinkling is lost
40 weeks 36 cm 3400 G
*Another table for further understanding

THE FETAL HEAD *Bones of the cranium are normally connected by thin layer
 First part that will pass the passage (pelvic cavity) of fibrous tissue that allows considerable shifting/sliding/
during delivery moving of each bone to accommodate to the shape of the
 Largest part of the baby to be delivered pelvis. During delivery, this skull bones overlap somehow to
 Represented by the skull and face accommodate to the shape of the maternal pelvis and we
call the MOLDING. After delivery, that sliding or molding
 Skull is made up of the following sets of bones:
goes back to its normal appearance
 Two frontal
 Two parietal
 Two temporal
 Upper portion of occipital bone
 Wings of sphenoid
 Separated by the following sutures (membranous
spaces)
 Frontal = between the 2 frontal bones
 Sagittal = between the 2 parietal bones
 Two coronal = between frontal & parietal
 Two lambdoid = between the posterior
margins of the parietal bones and upper
margin of the occipital bone
 Fontanel (bumbunan) – an area that is being
formed by several sutures; irregular space which is
enclosed by a membrane  Critical Diameters of the Fetal Head (2 point
 Greater or anterior fontanel – lozenge- diameter)
shaped space that is situated at the junction  It is customary to measure the newborn head
of the sagittal and the coronal sutures  Occipitofrontal Diameter = 11.5 cm
 Lesser or posterior fontanel – small from the root of the nose to the
triangular area at the intersection of the prominent portion of the occipital bone
sagittal and lambdoid sutures  Biparietal Diameter = left to right or R
 Temporal or casserian fontanel to L side of the head
 Bitemporal Diameter
 Occipitomental Diameter
 Suboccipitobregmatic Diameter

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  Circumference of the Fetal Head
 Plane of occipito-frontal diameter
 The greatest circumference of the fetal
head
 Passes usually through the vaginal
canal
 Averages 34.5 cm
 Plane of occipitobregmatic diameter
 the smallest circumference of the fetal
head
 averages 32 cm
PLACENTAL ROLE IN FETAL GROWTH
 Placenta – organ of transfer between the mother
and fetus
 What is being taken by the pregnant mother,
will pass through the digestive system,
metabolized by the liver, pushed to the
bloodstream, and go to the placenta, and
from the placenta to the fetus. It takes time.
The blood flow to the fetus is continuous; it
never stops.
 In that transfer, there is also transfer of
carbon dioxide and other metabolic waste
products from the fetus to the mother so the
placenta also serves as kidneys that clear the
fetal circulation.
 However, there are no direct connections
between the fetal blood (which is contained
in the fetal capillaries in the intravillous space
of the chorionic villi) and the maternal blood
(which remains in the intervillous space)
 Chorionic villi plus the intervillous space
functions as the fetus’ lung, GI tract and
kidney
 The Intervillous Space: Maternal Blood
 Substances transferred from mother to fetus
first enter the intervillous space and are then
transported to syncytiotrophoblast
 Substances transported from the fetus to the
mother are transferred from the syncytium
into the same space
 Placental Transfer
 Substances that pass from maternal blood to
fetal blood must traverse:
 Syncytiotrophoblast
 Stroma of the intravillous space
 Fetal capillary wall
 It does not function as a simple physical
barrier. Throughout pregnancy, the
syncytiotrophoblast passively permits,
facilitates and adjusts the rate and transfer of
wide range of substances to the fetus
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 Regulation of Placental Transfer
 In determining the effectiveness of the human
placenta as an organ of transfer, at least 10
variables are important:
1) Concentration of substance in the
maternal plasma
2) Rate of maternal flow
 If maternal flow is decreased (if the
mother is bleeding – vehicular
accidents; in cases of Placenta
Previa)
3) Area available for exchange- across the
villous trophoblast
 In some cases of small placenta
seen in mother with pre-eclampsia,
area available will be decreased so
the fetus might be growth
restricted.
4) Physical properties of tissue barrier
5) Capacity of the biochemical machinery
of the placenta
6) Amount of substance metabolized
 So if the mother has metabolic
problem (like DM, it might affect
the growth of the fetus
7) Area available for exchange- across the
fetal capillaries
8) Concentration of substance in the fetal
blood
9) Binding or carrier proteins
10) Rate of fetal blood flow
 Affected in cases of congenital
anomaly  small babies
 Mechanism of transfer
 Simple diffusion – mechanism of transfer of
low molecular weight compounds; oxygen,
CO2, water, most electrolytes, anesthetic
gases that we use in the delivery room
 Facilitated diffusion – for High molecular
weight like the Immunoglobulins
 Active transport – Immunoglobulins
 Placenta as the Fetal Lung: O2
 Transfer of oxygen across the placenta is
blood-flow limited but continuous
 Uteroplacental blood flow
 Oxygen delivery that is supplied (8 mL
O2/min/kg of fetal weight), is sufficient
only for 1-2 minutes, thus, should be
continuous
 Average oxygen saturation of
intervillous blood = 65 to 75 percent
 Partial pressure (PO2) = 30 to 35 mmHg
 There should be no interruption on the
umbilical cord(that conveys blood from
the placenta to the navel of the fetus)
 Placenta as the Fetal Lung: CO2
 Transfer of fetal CO2 is by diffusion
 More rapid than O2
 Near term, PCO2 in the umbilical artery = 50
mmHg or about 5 mmHg more than in the
maternal intervillous blood.
 Fetal blood has less affinity for CO2 than does
maternal blood
  Fetal Nutrition
 Largely dependent on maternal food intake,
nutritional status
 Fetal nutrition is largely dependent on
maternal food intake, nutritional status.
The maternal diet is translated into
storage forms that are made available to
meet the demands for energy, tissue
repair and new growth, including
maternal need s for pregnancy.
 You should regulate your diet depending
on your size. Why? So your baby will pass
through the maternal pelvis when the
time comes you need to give birth.
 Three major maternal storage depots – the
liver, muscle and adipose tissue
 Three major maternal storage depots –
the liver, muscle and adipose tissue and
the Storage hormone insulin are
intimately involved in the metabolism of
the nutrients absorbed from the
maternal gut
 Storage hormone insulin
 Maternal source of energy:
 Glucose as glycogen, mainly stored in liver
and muscle
 Amino acids as protein
 Free fatty acids from adipose tissue
 Glucose and fetal growth
 Glucose is a major nutrient for fetal growth
and energy
 Human placental lactogen (hPL), blocks the
peripheral uptake and use of glucose while
promoting the mobilization and use of free
fatty acids by maternal tissues
 Glucose transfer across cell membranes is
accomplished by a carrier-mediated, stereo-
specific, non-concentrating process of
facilitated diffusion.
 At least 14 separate glucose transport
proteins (GLUTs) have been discovered
 GLUT-1 and GLUT-3 = transports D-
glucose
 Located in the plasma membrane of the
microvilli of human
syncytiotrophoblast
 Free Fatty Acids and Triglycerides
 Neutral fat (triacyglycerols) does not cross
the placenta
 Glycerol crosses by simple diffusion
 Fatty acids are also synthesized in the
placenta
 Lipoprotein lipase is present on the maternal
but not on the fetal side
 The LDL particles from maternal plasma bind
to specific LDL receptors in the coated-pit
regions of microvilli on the maternal-facing
side of syncytiotrophoblast.
 Taken up by receptor-mediated endocytosis
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*The placental uptake and use of low-density lipoprotein
(LDL) is an alternative mechanism for fetal assimilation of
essential fatty acids and amino acids. The LDL particles from
maternal plasma bind to specific LDL receptors in the coated-
pit regions of the microvilli on the maternal-facing side of the
syncytiotrophoblast. The large LDL particle is taken up by a
process of receptor-mediated endocytosis.
 The apoprotein and cholesterol esters of LDL
are hydrolyzed by lysosomal enzymes in the
syncytium to give:
 Cholesterol for progesterone synthesis
 Free amino acids, including essential
amino acids
 Essential fatty acids, primarily linoleic
acid
 Linoleic acid or arachidonic acid or
both must be assimilated from
maternal dietary intake.
 Proteins
 Limited transfer of larger proteins across the
placenta
 Exceptions are:
 IgG
 Retinol-binding proteins
*Generally, there is very limited placental transfer of larger
proteins. There are important exceptions, for example,
immunoglobulin G (IgG) crosses the placenta in large amounts
via endocytosis via trophoblast Fc receptors. IgG is present in
approximately the same concentrations in cord and maternal
sera, but IgA and IgM of maternal origin are effectively
excluded from the fetus.
 Ions and trace metals
 Iodide transport
 carrier-mediated, energy requiring
active process
 placenta concentrates iodide
 Zinc in the fetal plasma also is greater than
those in maternal plasma
 Copper levels in fetal plasma are less than
those in maternal plasma
 This is important because copper-
requiring enzymes are necessary for
fetal development
 Placental Sequestration of Heavy Metals
 Heavy metal-binding protein
Metallothionein-1
 Expressed in human
syncytiotrophoblast
 Binds zinc, zopper, lead, and cadmium
 *The heavy metal-binding protein, metallothionein-1, is
expressed in human syncytiotrophoblast. This protein
binds and sequesters a host of heavy metals, including
zinc, copper, lead and cadmium
*The most common source of cadmium in the
environment is cigarette smoke. Cadmium levels in
maternal blood and placenta are increased with
maternal smoking, but there is no increase in cadmium
transfer into the fetus. Presumably, the low levels of
cadmium in the fetus are attributable to the
sequestration of cadmium by metallothionein(s) in
trophoblast. In the rat, data suggest that cadmium
reduces the number of trophoblast cells, leading to poor
placental growth
*Metallothionein also binds and sequesters copper
(Cu2+) in placental tissue, thus accounting for the low
levels of Cu2+ in cord blood (Iyengar and Rapp, 2001). A
number of enzymes require Cu2+, and its deficiency
results in inadequate collagen cross-linking and in turn,
diminished tensile strength of tissues. This may be
important because the concentration of cadmium in
amniotic fluid is similar to that in maternal blood. The
incidence of preterm membrane rupture is increased in
women who smoke. It is possible that cadmium
provokes metallothionein synthesis in amnion, causing
sequestration of Cu2+ and a pseudo copper deficiency.
 Vitamins
 Vitamins A (retinol)
 Greater concentration in fetus than
maternal plasma.
 Bound to retinol-binding protein and
prealbumin
 Retinol-binding protein is
transferred from the maternal
compartment across the
syncytium.
 Vitamins C (ascorbic acid)
 Transfer from mother to fetus is
accomplished by an energy-dependent,
carrier-mediated process
 Vitamins D (cholecalciferol), 1, 25-
dihydroxycholecalciferol
 Greater concentration in maternal
plasma than fetus
 1B-hdroxylation of 25-hydroxyvitamin
D3 takes place in placenta and in
decidua
FETAL PHYSIOLOGY
AMNIONIC FLUID/BAG OF WATER
 Early pregnancy
 Ultrafiltrate of maternal plasma
 Beginning 2nd trimester
 Similar to fetal plasma
 After 20 weeks
 Composed largely of fetal urine
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*The fetal kidneys start producing urine at 12 weeks, and by
18 weeks they are producing 7 to 14 ml/day
*Pulmonary fluid contributes a small proportion of the
amniotic fluid volume.
*”Pag maliit yung duckling, manamis namis pa yung
amniotic fluid, ultrafiltrate pa kasi. Kapag malaki na yung
sisiw, umiihi na sya kaya maalat alat, puro ihi pa.”
*First trimester – clear amniotic fluid
*Third trimester – certain color of amniotic fluid is
appreciable
 Volume of Amniotic Fluid
 The volume increases by 10 mL per week at 8
weeks
 and increases up to 60 mL per week at 21
weeks,
 then declines gradually back to a steady state
by 33 weeks
*When is the greater amount of amniotic fluid? Usually
in the 2nd trimester up to the first week of 3rd trimester.
*At 38-42 weeks, you expect amniotic fluid to be
lesser.
 Amniotic Fluid Functions:
 Serves to cushion the fetus – for
musculoskeletal development, protection
from trauma
 Maintains temperature
 EGF and EGF-like growth factors
(transforming growth factor-B) may promote
growth and differentiation of lungs and GIT.
Ingestion of AF into the GIT and inhalation
into the lung may promote growth and
differentiation of these tissues.
 Oligohydramnios – marked decrease in
the amniotic fluid
 Polyhydramnios – marked increase in the
amniotic fluid
 Role in Pulmonary Development
 Draining off amniotic fluid, chronically
draining pulmonary fluid through the
trachea, and by physically preventing the
chest excursion that mimic breathing 
PULMONARY HYPOPLASIA (Adzick and
assoc. 1984; Alcorn and coll, 1977)
 Animal studies have shown that
pulmonary hypoplasia can be produced
by draining off amniotic fluid, by
chronically draining pulmonary fluid
through the trachea, and by physically
preventing the chest excursion that
mimic breathing.
FETAL CIRCULATION
 Fetal blood does not need to enter the lungs to be
oxygenated
 Fetal heart chambers work in parallel, not in series
 The fetal circulation is substantially different from
that of the adult and functions until the moment of
birth, when it is required to change dramatically.
 For example, because fetal blood does not need to
enter the pulmonary vasculature to be oxygenated,
most of the right ventricular output bypasses the
lungs. In addition, the fetal heart chambers work in
parallel, not in series, which effectively supplies the
brain and heart with more highly oxygenated blood
than the rest of the body.
 Oxygen and nutrients materials required for fetal
growth and development are delivered to the fetus
from the placenta by the single umbilical vein. The
vein then divides into the ductus venosus and the
portal sinus. The DV is the major branch of the UV
and traverse the liver to enter the IVC directly. It does
not supply O2 to the intervening tissue, so it carries
with it well oxygenated blood directly to the heart. In
contrast the portal sinus carries blood to the hepatic
veins primarily on the left side of the liver, where
oxygen is extracted.
 The ventricles of the fetal heart work in parallel, not
in series. Well oxygenated blood enters the LV, which
supplies the heart and the brain, and less oxygenated
blood, enters the RV, which supplies the rest of the
body. These separate circulations are maintained by
the structure of the right atrium, which effectively
directs entering blood to either the LA or the RV,
depending on its oxygen contents. This separation of
blood according to its oxygen contents is facilitated
by the pattern of blood flow in the inferior vena cava.
 The well oxygenated blood tends to course along the
medial aspect of the IVC and the less oxygenated
blood stays along the lateral wall, facilitating their
shunting into opposite sides of the heart. Once this
blood enters the atrium, the configuration of the
upper interatrial septum or CRISTA DIVIDENS,
preferentially shunts the well oxygenated blood from
the medial side of IVC and the ductus venosus
through the foramen ovale into the left heart and
then to the heart and brain. After these tissues have
extracted needed nutrients and oxygen… the blood
then returns to the right heart through the SVC.
 90% of blood exiting the RV is then shunted thru the
Ductus arteriosus to the descending aorta.
 The less oxygenated blood coursing along the lateral
wall of the inferior vena cava enters the RA and is
deflected through the tricuspid valve to the RV. The
SVC courses inferiorly and anteriorly as it enters the
RA, ensuring that less well-oxygenated blood
returning from the brain and upper body will be
shunted directly to the RV. The ostium of coronary
sinus lies just superior to the Tricuspid valve so that
less oxygenated blood from the heart returns to the
right ventricle.
 As a result of this blood flow pattern, blood in the
right ventricle is 15 to 20 percent less than blood in the
LV
 The major portion, almost 90% of blood exiting the
RV is then shunted thru the Ductus arteriosus to the
descending aorta. The high pulmonary vascular
resistance and comparatively lower resistance in the
ductus arteriosus and the umbilical - placental
vasculature ensure that only about 15 percent of RV
output goes to the lungs. Thus, one third of the blood
passing through the DA is delivered to the body
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 After birth: Constricted are:
 Umbilical vessels
 Ductus arteriosus
 Foramen ovale
 Ductus venosus
 Hypogastric arteries obliterated within 3 to 4
days after birth - umbilical ligaments
 Umbilical vein forms the ligamentum teres
 Ductus constricts by 10 to 96 hours,
anatomically closed by 2 to 3 weeks, to
become ligamentum venosum
 After birth: Umbilical vessels Ductus
arteriosus Foramen ovale Ductus
venosus ---constrict or collapse
 The distal portion of the hypogastric
arteries undergo atrophy and obliterated
within 3 to 4 days after birth to become
the umbilical ligaments.
 While the intraabdominal remnants of
umbilical vein forms the ligamentum
teres
 The ductus venosus constricts by 10 to 96
hours and is anatomically closed by 2 to
3 weeks, resulting in the formation of
ligamentum venosum
FETAL BLOOD
 Hemopoiesis sites:
 Yolk sac – first in the very early embro
 Liver
 Bone marrow
 Hemopoiesis
 The first erythrocytes - nucleated and
macrocytic
 Mean cell volume = 180 fL and decreases to
105 - 115 fL at term
 Hemoglobin = 12 g/dL midpregnancy, 18
g/dL at term
 Erythropoiesis
 Fetal erythropoietin
 This process is controlled primarily by
fetal erythropoietin because maternal
erythropoietin does not cross the
placenta
 Fetal erythropoietin Production is influenced
by testosterone, estrogen, prostaglandin,
thyroid hormone and lipoprotein
 The fetal liver appears to be an important
source until renal production begin
  Fetal Blood Volume
 At term = 78ml/kg (Usher and associates,
1963)
 Volume of blood of fetal origin = 45ml/kg
(Gruenwald, 1967)
 Fetoplacental blood volume = 125 ml/kg
 Fetal Coagulation Factors
 Embryo = no hemostatic proteins
 Fetus at 12 weeks = starts producing normal,
adult-type, procoagulant, fibrinolytic and
anticoagulant proteins
 Maternal proteins does not cross the
placenta
 Factors that are low in cord blood are II, VII,
IX, X, XI, XII, XIII, and fibrinogen
FETAL IMMUNO RESPONSE
 Immunoglobulin G
 main Ig in the fetus, in the absence of
infection
 Maternal source transferred across the
placenta by receptor-mediated process in
syncytiotrophoblast
 IgG transport begins at 16 weeks, bulk
acquired during the last 4 weeks of
pregnancy, adult values are not attained until
3 years of age
 Transfer can be harmful like in D-antigen
isoimmunization resulting to HDN
 Immunoglobulin M
 Not transported from mother to fetus
 Increased levels are found in newborns with
rubella, CMV, or toxoplasmosis
 Immunoglobulin A
 Ingested in colostrum, provides protection
against enteric infections
 Lymphocytes
 B lymphocytes appear in liver by 9 weeks,
present in blood and spleen by 12 weeks
 T lymphocytes begin to leave the thymus at
about 14 weeks.
Despite this, the newborn responds poorly to
immunization, and especially poorly to bacterial
capsular polysaccharides. This immature response may
be due to either deficient response of newborn B cells
to polyclonal activators, or lack of T cells that
proliferate in response to specific stimuli
NERVOUS SYSTEM AND SENSORY ORGANS
 Spinal Cord Relation to Vertebral Column
 Embryo = entire length
 By 24 weeks = S1
 At birth = L3
 Adult = L1
 Myelination begins in the middle of gestation
 Synaptic function is developed by the 8th week
 Swallowing = 10 weeks
 Respiration = 14 to 16 weeks
 Rudimentary taste buds = 7 weeks
 Sucking ability = 24 weeks
 Ability to hear sound = 24 to 26 weeks
 Eye sensitivity = 28 weeks
 But perception of form and color is not
complete until long after birth
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GASTROINTESTINAL SYSTEM
 Swallowing begins at 10 to 12 weeks
 Effect on Amniotic Fluid Volume:
 Early pregnancy = little effect because the volume
swallowed is small compared with the total
 Late pregnancy = if swallowing is inhibited,
polyhydramnios is common; volume appears to be
regulated substantially by fetal swallowing, for
when swallowing is inhibited like in cases of
Tracheoesophageal fistula, hydramnios is common
 Meconium
 Fetal bowel contents consist of
glycerophospholipids, desquamated fetal
cells, lanugo, scalp hair, and vernix
 Dark greenish-black appearance is caused
by pigments, especially biliverdin
 Mechanism of passage:
 Normal bowel peristalsis in the mature
fetus or from vagal stimulation.
 When hypoxia stimulates
arginine vasopressin (AVP) release from
the fetal pituitary gland.
 Small bowel obstruction may lead to
vomiting in utero.
 Fetuses who suffer from congenital
chloride diarrhea may have diarrhea in
utero, which leads to hydramnios and
preterm delivery
URINARY SYSTEM
 Anatomical development
 Kidney and ureter = develop from
intermediate mesoderm
 Bladder and urethra = develop from
urogenital sinus
 Bladder = develops in part from the allantois
 Physiological development
 Kidneys = receive between 2 and 4 % cardiac
output. (Newborn receives 15 - 18 %)
 Renal vascular resistance is high and the
filtration fraction is low compared with
values in later life
 GFR = increases with GA from less than 0.1
mL/min at 12 weeks to 0.3 mL/min at 20
weeks.
 Hemorrhage or hypoxia, growth
restricted infants, infants of diabetic
mother results in decrease GFR and
output  lead to oligohydramnios
 Urine formation
 Starts at 12 weeks
 By 18 weeks = 7 to 14 mL/day
 At term = 27 mL/day or 650 mL/day
 ↑ Furosemide
  Uteroplacental insufficiency, fetal
stress
 Maternally administered Furosemide
increase fetal urine formation, whereas
uteroplacental insufficiency and other types
of fetal stress decrease it
PULMONARY SYSTEM  Corticosteroids and Fetal Lung Maturation
 Anatomical and morphological development  For premature deliveries: less than 32 weeks:
 Capacity for surfactant formation  Betamethasone 12 mg IM, 2 doses, 24
 The timetable of lung maturation and the identification of hours apart
biochemical indices of functional fetal lung maturity are of  Dexamethasone 5 mg IM, Q 12h x 4 doses
considerable interest. The structural and morphological  Possible S/E: neurodevelopmental anomalies
maturation of the fetal lung also is extraordinarily in the newborn, infection
important to proper lung function.
 If the lungs are immature at birth this may lead to the
*There is now clinical evidence that that
development of respiratory distress syndrome, and
complicates the course and treatment of other neonatal glucocorticosteroids administered in large amounts to
disorders. the women at certain critical times during gestation
 The presence of a sufficient amount of surface-active effect an increase in the rate of fetal lung maturation
material, or surfactant, in the amniotic fluid is evidence of
fetal lung maturity.
SEXUAL DIFFERENTIATION
 3 ways to determine gender
 Three stages of Lung Development (Moore,  Chromosomal/Genetic Gender
1983)  Genetic gender - XX or XY - is
 The lung development is interesting and uncanny. It established at the time of
is one of the earliest organ to develop and yet the fertilization/conception
latest to reach its maturity. The limits of viability,  Gonadal Gender
therefore, appear to be determined by the usual  At 6 weeks after conception - If a Y
process of pulmonary growth.
chromosome is present, the gonads
1. Pseudoglandular = 5th to 17th, there is
develop into testis. And the testes are
growth of the intrasegmental bronchial
responsible for the organization of the
tree
sexual duct system into a male
2. Canalicular = 16 to 25 weeks,
configuration and for the suppression of
bronchiole formation, the bronchial
the paramesonephric (mullerian) system.
cartilage plates extends peripherally.
 Production of: at 8th week AOG: During
Terminal bronchioles give rise to several
the 8th week of gestation the secretion of
respiratory bronchioles
testosterone and antimullerian hormone
3. Terminal Sac = pulmonary alveoli; type
(AMH) from the testes steers the further
II cells begin to produce surfactant.
development of the rest of the genital
This is the final stage, during which
tracts
alveoli give rise to primitive pulmonary
 Testosterone (secreted by Leydig
alveoli, called the terminal sacs.
cells)
 Clinical correlation:
 antimullerian hormone/AMH/MIF
 (+) renal agenesis
(secreted by Sertoli cells (acts
 No amniotic fluid is present from the
locally in suppressing the mullerian
beginning of lung growth
duct system, and testosterone acts
 Fetus with membrane ruptures before
systemically, causing differentiation
20 weeks
of the mesonephric duct system and
 Normal bronchial branching and
affecting male development of the
cartilage development but has
urogenital tubercle, urogenital sinus,
immature alveoli
and urogenital folds)
 Membrane ruptures after 24 weeks
 Phenotypic Gender
 Little long term effect on pulmonary
 After establishment of the gonadal
structure
gender, phenotypic gender develops
 Surfactant
very rapidly
 A substance formed specifically in the type II
 Male phenotypic sexual differentiation
pneumocytes that line the alveoli
is directed by the function of the fetal
 Uncoils from the lamellar bodies, and spreads
testis
to line the alveolus
 In the absence of a testis, female
 prevents the collapse of terminal sacs or
differentiation ensues irrespective of
alveoli during expiration
the genetic gender
 Composition:
 Put it in another way, development and
 Protein (10%)
differentiation of the internal and
 Lipid (90%)
external genitalia to male phenotype is
 80% are phosphatidylcholines
dependent on testicular function. On
(lecithins)
the contrary, fetal ovary is not required
 The principal active lecithin is
for female sexual differentiation
dipalmitoylphosphatidylcholine
(DPPC) – 50%
 Phosphatidylglycerol (PG) – 8 to
15% (Its precise role is unclear
because newborns without
phosphatidylglycerol usually do well)
 Phosphatidylinositol (PI)

8|DLSHSI Medicine Batch 2016

  Fetal Gender
 1963 - Carr quoted 106 males to 100 females
 1998 - Davis reported a significant decline in
male births since 1950 in Denmark, Sweden,
Netherlands, U.S., Germany, Norway and
Finland
 1997 - In Canada, the proportion of male has
dropped by 2.2 male births per 1000 live
births. In the Atlantic region, the decline was
5.6 male per 1000
 If you will think about it, there should be equal
gender ratio at the time of fertilization because
there are equal number of X and Y bearing
spermatozoa. But that is not the case, and
many factors have been shown to contribute to
gender ratios at conception, like differential
susceptibility to environmental exposures as
well as medical disorders. Couples with a large
age discrepancy are more likely have a male
offspring. Whatever the cause, it is impossible
to determine the primary gender ratio
 Differentiation of Mullerian Ducts
 Early in embryonic life, two sets of paired
genital ducts develop in each sex: the
mesonephric (Wolffian) ducts and the
paramesonephric (Mullerian) ducts. The
mesonephric duct development precedes the
paramesonephric duct development.
 In the presence of ovaries or of gonadal
agenesis, the mesonephric ducts regress, and
the paramesonephric ducts develop into the
female genital tract. This process begins at
about 6 weeks and proceeds in a cephalad to
caudal fashion
 mesonephric (Wolffian) ducts
 paramesonephric (Mullerian) ducts
 The more cephalad portions, which
open directly into the peritoneal cavity,
form the fallopian tubes.
 The fused portion, or uterovaginal
primordium, gives rise to the
epithelium and glands of the uterus and
cervix
 Endometrial stroma and myometrium
are derived from adjacent mesenchyme
 Three-stage process for fusion of the two
Müllerian Ducts
 1st STAGE (10th week)
 Short, taking place at the beginning of
the tenth week. The medial aspect of
the more caudal portions of the two
ducts fuse, starting in the middle and
9|DLSHSI Medicine Batch 2016
then proceeding simultaneously in both
directions. In this way a median septum
is formed.
 The 2 paramesonephric ducts (red)
FUSE in the midline (caudal-cephalad
direction)
 2nd STAGE (10th-13th weeks)
 The second stage continues from the
tenth to the thirteenth week and occurs
because of a rapid cell proliferation and
the filling in of the triangular space
between the two uterine cornua. In this
way a thick upper median septum is
formed. This is wedge like and gives rise
to the usual external contour of the
fundus. At the same time the lower
portion of the median septum is
resorbed, unifying the cervical canal
first and then the upper vagina.
 RESORPTION of lower median septum,
unification of cervical canal and upper
vagina
 3rd STAGE (13th-20th weeks)
 The third stage lasts from the
thirteenth to about the twentieth week.
In this stage the degeneration of the
upper uterine septum occurs, starting
at the isthmic region and proceeding
cranially to the top of the fundus. In this
way a unified uterine cavity is formed.
 RESORPTION of upper septum,
unification uterine cavity
 Vaginal Development
 from paired solid outgrowths of endoderm of
the urogenital sinus-the sinovaginal bulbs
 These grow caudally as a solid core toward
the end of the uterovaginal primordium -
constitutes the fibromuscular portion of the
vagina
 The sinovaginal bulbs then canalize to form
the vagina.
 Abnormalities in this process may lead
to either transverse or horizontal
vaginal septa.
 The junction of the sinovaginal bulbs with the
urogenital sinus remains as the vaginal plate,
which forms the hymen.
 This remains imperforate until late in
embryonic life, although occasionally,
perforation does not take place
completely (imperforate hymen). It is
different from INTACT HYMEN!
 HOMOLOGUES

EMBRYONIC STRUCTURE MALE FEMALE

Labioscrotal swelling Scrotum L majora
Urogenital folds Ventral portion of penis L minora
Phallus Penis Clitoris
U bladder U bladder
Prostate Urethral and Paraurethral
Urogenital sinus Prostatic utricle Vagina
Bulbourethral glands Greater Vest gland
Seminal colliculus Hymen
Hydatid of Morgagni
Paramesonephric Appendix of testes
Uterus, cervix, FT
Appendix of epididymis Appendix vesiculosis
Mesonephric Ductus epididymis Duct of epoophoron
Ductus deferens Gartner’s Duct
*Table 1-2 categorizes the adult derivatives and residual remnants of the urogenital structures in both the male and the female.

 Gender assignment at birth

 Basic requirements for gender assignment
1. Karyotypic sex
2. Gonadal sex
3. Hormonal milieu
4. Anatomy
5. Possibilities for surgical correction
 The first thing that parents want and even the birth attendant wants to know during the delivery is the gender of
the infant. If the genitalia of the newborn are ambiguous, that would be a profound dilemma. It is no longer believed
that the proper functional assignment for newborns with genital ambiguity can be made promptly in the delivery
room.

 Preliminary diagnosis
 Physical examination
 Ultrasound evaluation:
 (+) uterus = consider Female Pseudohermaphroditism, testicular or gonadal dysgenesis or True
hermaphroditism
 (-) uterus = Male Pseudohermaphroditism

-FIN-

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