PREGNANCY AND

LACTATION

Importance of physiology of pregnancy

It is concerned with
- the nutrition to the growing fetus
- the maternal changes needed to provide a
adequate nutrition to the growing fetus
- the maternal changes required for child
birth and lactation

MATURATION AND
FERTILIZATION OF OVUM

In ovary ovum is in primary oocyte stage

Shortly before release it releases 1st polar

body and becomes secondary oocyte

At this stage ovum is ovulated into

abdominal cavity and it enters the
fimbriated end of one of fallopian tube

Entry of ovum into fallopian tube

-After ovulation the ovum along with attached
granulosa cells k.a. corona radiata is expelled
into peritoneal cavity to enter fallopian tubes
-The fimbriated ends of fallopian tubes are
lined by ciliated epithelium and these cilia are
activated by estrogen from ovaries
-The cilia beat towards the ostium of fallopian
tubes helping ovum to enter ampulla of
fallopian tubes
-The ovum is then held up at ampullary
isthmic junction for 2 to 3 days

During this time :

-if no fertilization occurs the ovum degenerates
and dies

-if fertilization takes place , cell division occurs

until blastocyst is transported into uterus this
is achieved by relaxation of sympathetically
innervated muscle of the isthmus assisted by
ciliary action towards uterus

Transport of spermatozoa from the vagina to ampulla

-After intercourse millions of sperms are deposited in vagina but
only a few sperms are transported within 5 to 10 min upwards
from vagina through uterus to ampullae of fallopian tubes
-This transport is assisted by contractions of uterus and fallopian
tubes caused by prostaglandins in seminal fluid and oxytocin
released by post pituitary gland of female
-Fertilization occurs in ampulla of either of fallopian tubes
-The sperm has to pierce corona radiata and zona pellucida with
acrosomal reaction to reach ovum
-Once the sperm has entered ovum the oocyte divides again to
form mature ovum, the female pronucleus and the sperm forms
the male pronucleus each having 23 unpaired chromosomes
-These then unite to form fertilized ovum

-sperm binds to a sperm receptor called ZP3 in the zona

and this is followed by Acrosomal reaction
-Acrosomal reaction involves the breakdown of
acrosome, release of enzymes like Acrocin which
facilitates penetration of sperm into zona pellucida
-one sperm reaches the ovum membrane, fusion to
membrane is mediated by Fertilin a protein present on
surface of sperm head
-the fusion provides a signal that initiates development
-the fusion also sets off a reduction in membrane
potential of ovum that prevents polyspermy i.e.
fertilization of ovum by more than one sperm

Transport of fertilized ovum in the fallopian tube

After fertilization 3 to 5 days are required to
transport fertilized ovum into uterine cavity
This is aided by epithelial secretion, action of ciliated
epithelium that lines the tube and weak contractions
of fallopian tube.
Increased progesterone secretion causes tubular
relaxing effect that also allows entry of fertilized
ovum into the uterus
This delayed transport of fertilized ovum through the
fallopian tube allows several cell divisions to occur
and the ovum is now called a blastocyst consisting of
100 cells
During this stage large secretions formed by fallopian
tubes secretory cells nourish developing blastocyst

Implantation of Blastocyst in the Uterus

After reaching uterus, Blastocyst remains in uterine
cavity for 1-3 days before implantation
During this time it is nourished by uterine secretion
called uterine milk
Implantation results from action of trophoblast cells,
that develop over surface of blastocyst, the outer layer
called as syncytiotrophoblast and inner called as
cytotrophoblast
These cells secrete proteolytic enzymes that digest and
liquefy adjacent uterine endometrium
Once implantation takes place, the trophoblast cells and
adjacent cells from uterine endometrium proliferate
rapidly to form the placenta

Early nutrition of embryo

Progesterone: secreted by corpus luteum converts the

endometrial stromal cells into large swollen cells
containing extra quantities of glycogen, proteins, lipids
and minerals
Later when conceptus implants in the endometrium the
continued secretion of progesterone causes the
endometrial cells to swell more and store more
nutrients. These cells are called decidual cells
The trophoblast cells invade the decidua, digesting and
imbibing it, the stored nutrients in the decidua are used
by embryo for growth and development upto 8 wks
Placenta also begins to provide nutrition after 16th day
beyond fertilization

Placenta

The trophoblastic cords from the blatocyst are

attaching to uterus, blood capillaries from
embryo also grow into chords.
By 16th day blood starts to be pumped by heart
of embryo
At the same time blood sinuses with maternal
blood starts to develop around trophoblastic
cords
The trophoblastic cells send out more
projections which become placental villi into
which fetal capillaries grow

The placenta combines the function of

alimentary tract, kidneys and lungs for fetus
In placenta the fetus blood flows through two
umbilical arteries into capillaries of villi then
back through single umbilical vein into fetus
The mothers blood flows from her uterine
arteries into maternal sinuses that surround
villi and then back into uterine veins
The total surface area of villi of mature
placenta is only a few square meters but
exchange of nutrients via diffusion is enormous

Functions of placenta
1.Diffusiom of oxygen through placental membrane
-Oxygen passes through simple diffusion
- Mean Po2 in maternal blood is 50mmHg and mean
Po2 in fetal blood is 30mmHg so mean pressure
gradient for diffusion for oxygen is 20mmHg
-Reasons why fetus gets sufficient O2 inspite of low
Po2 of 30mmHg
a. Fetal hemoglobin
b. Hemoglobin concentration of fetal blood is 50%
greater than maternal blood
c. Double Bohrs effect

2.Diffusion of carbon dioxide through the

placental membrane
- CO2 is continually being formed in fetal
tissues
- Pco2 of fetal blood is 2 to 3mmHg higher
than maternal blood
-This small pressure gradient is more than
sufficient to cause diffusion of CO2
-Solubility of CO2 in placental membrane is
20 times more than solubility of oxygen

3.Diffusion of food stuffs through the placenta

-Diffusion is same as that of oxygen
-Facilitated diffusion of glucose occurs via
placental membrane
-Glucose level in fetal blood is 20 to 30% less
than maternal blood
-High solubility of fatty acids facilitates their
diffusion across the placental membrane
- Potassium, sodium and chloride ions diffuse
with relative ease from maternal blood to fetal
blood

4.Excretion of waste products through the

placental membrane
-The excretory products from fetal blood
diffuses through placental membrane into
maternal blood and are excreted along with
excretory products of mother
- These include urea, uric acid and creatinine
-The concentration of excretory products is
greater in fetal blood than in maternal blood

Hormonal factors in pregnancy

5.During pregnancy placenta forms large
quantities of hormones like:
- Human Chorionic Gonadotropin
-Estrogens
-Progesterone
-Human Chorionic Somatotropins

HCG

Secreted by syncytiotrophoblast cells of fertilized ovum

Secretion is first measured in maternal blood 8 to 9
days after ovulation
Rate of secretion rises rapidly reaching maximum at 10
to 12 wks of pregnancy and then declining to lower
value by 16 to 20 wks
It is a glycoprotein with molecular weight of 39000
It is made of and subunits
Functions like luteinizing hormone
It can be measured in blood by Radioimmunoassay as
early as 6 days after conception
Its presence in the urine in early pregnancy is basis of
pregnancy test. It can be detected in urine as early as
14 days after conception

Functions of HCG:
-prevents involution of corpus luteum
-causes corpus luteum to secrete extra
quantities of estrogen and progesterone
-these hormones help in continuation of
pregnancy by preventing menstruation and
converting endometrial cells into decidual cells
-it maintains corpus luteum till placenta starts
secreting sufficient quantities of estrogen and
progesterone
-it also exerts interstitial cell-stimulating effect
on testes of male fetus to secrete testosterone
which causes fetus to grow male sex organs

Pregnancy tests
1.Immunological tests:
Principle: antiserum to HCG can detect the presence of
HCG in urine and serum of pregnant women by
Complement fixation test, Haemagglutination,
Precipitin test.
Procedure: the presence of HCG is detected by an
immunological reaction between HCG adsorbed on
latex particles and HCG antiserum.
a .A drop of urine of non-pregnant women (contains no
HCG) +a drop of HCG antiserum (contains HCG
antibodies) leads to no neutralization of HCG
antiserum, so will produce agglutination when mixed
with HCG- coated latex

b .A drop of urine from a pregnant women (contains HCG)+ a

drop of HCG antiserum leads to neutralization of antiserum HCG
therefore will produce agglutination when mixed with HCG
coated latex
2. Measurement of HCG in blood by Radioimmunoassay
- Antibody for HCG is prepared in a lower animal
-Mixture of fluid in which hormone is to be measured + small
quantity of antibody+ HCG tagged with radioactive isotope is
made
-The sample HCG and the tagged HCG compete for binding sites
on antibody
-After binding has reached equilibrium antibody-hormone is
separated and measured by radioactive counting technique

Estrogen

Secreted by syncytiotrophoblast cells of placenta

Secretion increases 30 times the maternal level
towards end of pregnancy
It causes enlargement of mothers uterus
Enlargement of mothers breast and breast ductal
system
Enlargement of mothers female external genetalia
Relaxes pelvic ligaments of mother to make more
room for growing fetus
It also helps overall development of fetus during
pregnancy

Progesterone

Secreted by syncytiotrophoblast cells of placenta

There is 10 fold increase in its secretion throughout
pregnancy
It helps in nutrition of morula and blastocyst by
increasing secretions of fallopian tubes and uterus
It cause decidual cells to develop in endometrium
It decreases contractility of uterus preventing
spontaneous abortion
It helps estrogen prepare mothers breast for lactation

Human Chorionic Somatomammo

tropin

It is a protein having mol wt of 38000

Secreted by placenta at about 5th wk of
pregnancy and its secretion gradually increases
throughout pregnancy
It helps in development of breast and lactation
It has weak action similar to growth hormone
It causes decreased insulin sensitivity and
utilization of glucose in mother thereby making
large amounts of glucose available for fetus

Other Hormonal factors in

pregnancy

Pituitary secretion: pituitary secretion of

corticotropin, thyrotropin and prolactin increases.
Secretion of FSH and LH decreases
Corticosteroid secretion: increase in glucocorticoid
secretion and aldosterone secretion
Thyroid secretion: mothers thyroid gland enlarges
upto 50% and secretion of thyroxine also increases
upto 50%
Parathyroid secretion: increase in secretion of
parathyroid hormone during pregnancy and lactation
Relaxin secretion: causes relaxation of pelvic
ligaments

Fetoplacental unit

The fetus and placenta interact in formation of steroid

hormones
The placenta synthesizes pregnenolone and progesterone
from cholesterol
Progesterone enters fetal circulation and gets converted
into Cortisol and corticosterone
Pregnenolone enters fetus to form
dehydroepiandrosterone sulphate (DHEAS ) and 16hydroxy dehydroepiandrosterone sulphate (16OHDHEAS)
DHEAS and 16-OHDHEAS are transported back to
placenta to form estradiol and estriol

PLACENTA

FETAL ADRENAL

CHOLESTEROL

DHEAS
PREGNENOLONE
PROGESTERONE

16-OHDHEAS
CORTISOL
CORTICOSTERONE

ESTRADIOL
ESTRIOL

DHEAS
16-OHDHEAS

Response of mothers body to

pregnancy

Weight gain: the average weight gain is 24

pounds
-7 pounds is fetus
-4 pounds is amniotic fluid
-2 pounds uterus
-2 pounds breast
-9 pounds increase in mothers weight out of
which 6 pounds are of extra cellular fluid and 3
pounds of fat accumulation

Metabolism during pregnancy:

-BMR increases by 15% during latter half of
pregnancy due to increased secretion of Thyroxine,
Adrenal Cortical hormones and sex hormones
-nutritional requirements increase most being in 3rd
trimester
-greatest growth of fetus occurs in 3rd trimester
-if appropriate nutritional elements are not present in
pregnant women's diet a number of nutritional
deficiencies can occur

Changes in maternal circulatory system:

-625ml of blood flows through the maternal
circulation of placenta each minute during last
month of pregnancy
-cardiac output of mother increases by 30 to
40% by 27th wk of pregnancy and falls only a
little by end of pregnancy
-maternal blood volume increases to 30% till
term the increase is more towards second half
of pregnancy. The cause is mainly hormones
like aldosterone and estrogen causing retention
of fluid by kidneys

Changes in maternal respiration:

-due to increased BMR the amount of oxygen
used increases to 20% above normal
-mothers minute ventilation increases to about
50%
-increased levels of progesterone during
pregnancy increase sensitivity of respiratory
centre to carbon dioxide thus increasing
minute ventilation
-the growing fetus decreases the diaphragm
movements so the respiratory rate is increased
to maintain extra ventilation

Changes in maternal urinary system:

-the rate of urine formation is increased due to
increased intake and increased load of
excretory products
-reabsorptive capacity for sodium, chloride
and water by renal tubules increases by 50%
due to production of steroid hormones by
placenta and adrenal cortex
-GFR also increases by 50%which increases the
rate of water and electrolyte excretion in urine

Amniotic fluid and its formation:

-volume is 500ml to 1 liter
-water in amniotic fluid is replaced every 3 hrs
-electrolytes are replaced every 15 hrs
-a portion of fluid is derived from renal excretion
of fetus
-the total volume is regulated by amniotic
membranes and fetal excretion

Toxemia of pregnancy:
-about 5% of pregnant women have raised BP during
last few months of pregnancy
-leakage of large amount of proteins in urine
-also called as Pre Eclampsia
-there is excess of salt and water retention by mothers
kidneys
-arterial spasm occurs in kidneys ,liver and brain
-renal blood flow and GFR both are decreased
-Eclampsia is similar condition with extreme degree of
vascular spasm throughout the body leading to
seizures
-without treatment fetal and maternal mortality
increases

Parturition

Parturition simply means birth of baby

Towards end of pregnancy uterus becomes

progressively excitable until it develops strong
contractions and the baby is expelled

Hormonal and progressive mechanical

changes are responsible for increased
excitability of uterus

HORMONAL FACTORS
a)

Ratio of estrogens to progesterone

b)

Effect of oxytocin on the uterus

c)

Effect of fetal hormones on uterus

Ratio of estrogens to progesterone

Progesterone inhibits uterine contractility during pregnancy

Estrogens have definite tendency to increase uterine
contractions. It makes uterus more excitable, increases
number of gap junctions between myometrial cells and causes
production of prostaglandins
Estrogen increases oxytocin receptors in myometrium and
decidua
Both estrogen and progesterone are secreted in progressively
greater quantities throughout pregnancy, but from 7th month
onwards estrogen secretion continues but secretion of
progesterone remains constant or decreases slightly
Estrogen to progesterone ratio increases sufficiently towards
end of pregnancy increasing contractility of uterus

Effect of oxytocin on uterus

Oxytocin is secreted by neurohypophysis that

specifically causes uterine contractions
The uterine muscles increases its oxytocin receptors
during latter few months of pregnancy
The rate of secretion of oxytocin increases during
labor
Labor is prolonged in hypophysectomized animals
Experiments in animals indicate that irritation or
stretching of cervix increases secretion of oxytocin

INCREASE IN OXYTOCIN RECEPTORS

PROSTAGLANDINS
UTERINE CONTRACTIONS
DILATATION OF CERVIX AND
DISTENTION OF VAGINA
STIMULI FROM CERVIX
AND VAGINA
INCREASED SECRETION
OF OXYTOCIN

Effect of fetal hormones on uterus

The fetus pituitary gland secretes increasing

quantities of oxytocin that could increase
uterine contractions
The fetus adrenal glands secrete large
quantities of Cortisol which is also a uterine
stimulant
The fetal membranes release prostaglandins in
high concentration at time of labor. This also
increases the uterine contractions

Mechanical factors
a. Stretch of uterine musculature:
-simply stretching smooth muscle organs
increases their contractility
-Intermittent stretch of uterus by movements
of fetus elicits smooth muscle contractions
-twins are born on an average 19 days earlier
than single child emphasizes the importance of
mechanical stretch

b. Stretch or irritation of the cervix:

- stretching of uterine cervix is very important in
eliciting uterine contractions
-to induce labor obstetricians rupture the
membranes so that the head of baby stretches the
cervix
-The mechanism by which cervical irritation
excites uterus is not known
-stretching or irritation of nerves in cervix
initiates reflexes to the body of uterus
-it can also simply be due to myogenic
transmission of signals from cervix to uterus

Onset of labor
A positive feedback theory:
-Braxton hicks contractions- weak and slow rhythmical
contractions
-Labor contractions- stronger contractions towards end of
pregnancy
-Positive feedback theory suggests that stretching of cervix by
fetal head finally becomes great enough to elicit a strong reflex
increase in contractility of uterine body. This pushes the baby
forward which stretches the cervix even more and initiates
more positive feedback to uterus
-Labor contractions obey all principles of positive feedback
-The positive feedback increases due to cervical stretching and
secretion of oxytocin
-Labor contractions elicit neurogenic reflexes in spinal cord to
abdominal muscles causing intense contractions of these
muscles

Mechanics of parturition

The uterine contractions during labor begin at top of

fundus and spreads over the body of uterus
The intensity of contractions is maximum at fundus
and body and minimum at lower segment adjacent to
cervix, therefore each contractions pushing baby
down towards cervix
The frequency and intensity of contractions keeps on
increasing with short relaxation between contractions
The combined uterine and abdominal contractions
cause a downward force of 25 pounds on fetus during
each strong contraction

The labor contractions are intermittent because strong

contractions impede blood supply to placenta and can
lead to death of fetus if continuous
The head of fetus is first to be expelled in most cases.
The acts as a wedge to open structures of birth canal
First stage of labor involves progressive dilation of
cervix till it becomes as large as fetus head.. It lasts for
8 to 12 hrs in first pregnancy, but few minutes after
many pregnancies
Second stage of labor lasts from cervical dilation to
delivery of baby. It lasts for 30 min in 1st pregnancy to
1 min after many pregnancies

Separation of placenta

Uterus contracts after delivery of baby for 10

to 45 min. This causes shearing effect between
uterine wall and placenta leading to separation
of placenta
This causes opening of placental sinuses and
bleeding.
Amount of blood loss is 350ml
The contraction of uterus and prostaglandins
released cause the blood vessels to constrict
and prevent excessive blood loss

Labor pains

The painful uterine contractions during labor

It is caused by hypoxia of uterine muscles
resulting from compression of blood vessels
Hypogastric nerves which carry visceral
sensory fibers from uterus are responsible
During second stage of labor cervical
stretching, perineal stretching and stretching
and tearing of structures of vaginal canal cause
pain

Involution of uterus

It takes 4 to 5 wks after parturition for uterus to come

back to its normal size. This is called as involution
If mother lactates its size becomes as small as it was
before pregnancy
This happens due to suppression of pituitary
Gonadotropin and ovarian hormone secretion during
first few months of lactation
During involution lochia a vaginal discharge is
produced for 10 days which is bloody to start with and
then serous in nature
After this endometrium becomes re-epithelialized and
returns to normal

Lactation
Lactation includes:
1.Development of breast- function of
estrogens and progesterone
2.Initiation of lactation- function of prolactin
3.Ejection (let down ) process in milk
secretion- function of oxytocin

Development of breast
This involves:
1.Growth of ductal system-role of estrogens:
-Tremendous quantities of estrogens secreted
by placenta during pregnancy cause ductal
system of breast to branch and grow
-Stroma of breast also increases with deposition
of fat
-Other hormones responsible are GH,
Prolactin, Adrenal glucocorticoids and Insulin

2.Development of lobule -alveolar systemRole

of progesterone
- Final development of breasts into milk
secreting organs requires progesterone
-Progesterone acts synergistically with other
hormones like estrogen to cause additional
growth of breast lobules, budding of alveoli and
development of secretory characteristics in cells
of alveoli
-These changes are analogous to effects of
progesterone on uterine endometrium

Initiation of lactation-function of
prolactin
- Prolactin is secreted by ant pituitary gland
- It promotes milk secretion
- Its concentration increases in blood after 5th wk of pregnancy
until birth of baby when it is 10 to 20 times non pregnant level
- Estrogen and progesterone though imp for breast development
also inhibit the actual secretion of milk
-HCG secreted by placenta also has lactogenic properties
-Colostrum is fluid secreted in last few days before and first few
days after parturition
-It has same concentration of glucose and proteins like milk but
no fat

-After the birth of baby, there is sudden fall in

concentration of estrogens and progesterone. This
allows prolactin to take over its natural milk
promoting role
-This milk secretion also requires adequate background
secretion of hormones like GH, Cortisol, Parathyroid
hormone and Insulin
-These provide amino-acids, glucose, fatty acids and
calcium required for milk formation
-After birth of baby the basal level of prolactin
secretion returns to non pregnant level after a few
weeks
-Each time mother nurses child nervous signals from
nipple to hypothalamus cause 10 to 20 fold surge in
prolactin secretion which lasts for about 1hr

Hypothalamic control of prolactin

secretion

Hypothalamus plays important role in

prolactin production
It mainly inhibits prolactin production
This is done by prolactin inhibitory hormone
secreted by Arcuate nucleus of hypothalamus
It can decrease prolactin secretion upto 10 fold
It also secretes a Prolactin releasing factor
which intermittently increases prolactin
secretion( under special conditions when baby
suckles)

Effect of lactation on menstrual

cycle

Women who do not nurse their infants usually have their periods
by 6 wks after delivery
Women who nurse regularly have amenorrhea for 25-30 wks
Nursing stimulates prolactin secretion which inhibits GnRH
secretion, inhibits the action of GnRH on pituitary, and
antagonizes action of gonadotropins on ovaries
This suppresses secretion of FSH and LH
Ovulation and ovarian cycle are inhibited and ovaries are
inactive, so estrogen and progesterone output falls to low levels
Also 50% of cycles in first 6 months after resumption of mensus
are anovulatory

Ejection ( let-down ) process in milk

secretion function of oxytocin

Milk that is secreted continuously in alveoli of breast does not

flow easily into ductal system
The milk must be ejected from alveoli into ducts before the
baby can obtain it
This ejection is caused by a neurogenic and hormonal reflex
that involves oxytocin hormone
When baby suckles sensory impulses are transmitted via
somatic nerves from nipples to mothers spinal cord and then to
hypothalamus
This causes secretion of oxytocin and prolactin
The oxytocin is carried in blood to breasts where it causes
myoepithelial cells to contract thereby expressing milk from
alveoli into ducts
Within 30sec to 1min after baby begins to suckle, milk begins to
flow

Composition of milk
HUMAN
MILK(%)
WATER
FAT
LACTOSE
CASEIN
LACTALBUMIN AND OTHER
PROTEINS
ASH

COWS MILK(%)

88.5

87.0

3.3

3.5

6.8

4.8

0.9

2.7

0.4
0.2

0.7
0.7

Lactation metabolic drain on

mother

At the height of lactation in human mother 1.5

liters of milk is formed everyday
At this rate about, 50gms of fat, 100gms of
lactose and 2 to 3gms of calcium phosphate
enter the milk everyday
This is a great metabolic drain on mothers
body
The nursing mother should have nutritious
diet to maintain adequate nutrition of her
body

Antibodies and other Anti-infectious

Agents in Milk

Mothers milk provides the baby with adequate

nutrition and also provides protection against
infections
Many antibodies and anti-infectious agents are
secreted in milk
Different types of white blood cells like
neutrophils and macrophages are secreted
which prevent child from deadly bacterial
infections