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Physiology of

pregnancy
dr. Fatimah Masyhur
OUTLINE
PREFACE

HAEMATOLOGY CARDIOVASCULAR

PHYSIOLOGY IN
PREGNANCY

GASTROINTESTINAL
TRACK
RESPIRATORY

URINARY
TRACK
PREFACE
CARDIOVASCULAR SYSTEM
PHYSIOLOGY IN PREGNANCY
Metabolic demands of the
mother and fetus ↑ and
ensure adequate Body
uteroplacental circulation for
fetal growth
Adapted
and development
Physiological changes
in the cardiovascular
system
Maternal
Haemodynamics
Changing

Plasma Volume
Cardiac Outoput Blood Pressure Heart Rate Contractility
& RBC

Increase Decrease Increase Not Change Increase


Haemodynamic Changing
Pregnancy Vasodilatation
5 weeks-full
placentation &
Systemic complete development
Kidney
Vasculature of uteroplacental
circulation
Systemic Vascular
Resistance ↑

Vasodilatation of GFR & Renal Creatinine Serum,


Kidney Plasma Flow ↑ Urea, Uric Acid ↑
In the first trimester, there is a
substantial decrease in
peripheral vascular resistance,
which decreases to a nadir
during the middle of the
second trimester with a
subsequent plateau or slight
increase for the remainder of
the pregnancy The decrease is
≈35% to 40% of baseline
Cardiac Output Changing
Cardiac Measuring
Echocardiography And
Cardiac Magnetic
Left Lateral Decubitus
Position
Output Resonance Imaging
Comparative study of 34 normal
pregnant women, images taken in 3rd
Trimester
Trimester I Sharpest Rise
Increase In Left
Ventricular End-
Week 24 → Increase
diastolic Volume, An
Trimester II Increase
Up To 45% Increase In Left
Ventricular Mass, And
An Increase In
Cardiac Output
Trimester III Constant/decrease
During Pregnancy
Blood Pressure Changing
Blood decrease in arterial
pressures
Pressure
Systolic Blood Mean
Central SBP
Pressure Arterial Pressure

Arterial pressures decrease to


a nadir ↓ More than SBP
Trimester II (dropping 5–10 mm Hg below
baseline)

Trimester II Increase

Brachial SBP
Remained Lower Than
Return Close To Preconception Values But
Post Partum Preconception Similar To Early Pregnancy
Levels
Central SBP
Heart Rate Changing
Increases During
Heart Rate Normal Gestation

Trimester I Increase

Increases
Progressively
20% to 25%
maximum
Trimester II change
Throughout The increase over
Pregnancy By 10 To
20 Bpm baseline
maximum heart
Trimester III rate
Plasma Volume Changing
Plasma Increases During
Normal Gestation
Volume
Trimester I Increase

Increases
Progressively
20% to 25%
maximum
Trimester II change
Throughout The increase over
Pregnancy By 10 To
20 Bpm baseline
maximum heart
Trimester III rate
Haemodynamic Changing
plasma volume
Pregnancy expansion and fetal
growth

Erythrocyte life Erythropoiesis Blood Volume


span decreased Increased Increase

Plasma Volume Increase


Physiological Anemia Proportionally than
RBC mass
Several
Cardiovascular
Changes in
Pregnancy
RESPIRATORY SYSTEM
PHYSIOLOGY IN PREGNANCY
Metabolic demands of the
mother and fetus ↑ and
ensure adequate Body
uteroplacental circulation for
fetal growth
Adapted
and development
Physiological changes
in the Respiratory
system
Maternal
Respiratory
Changing

O2 Residual Minute Respiratory Functional


Tidal Volume FEV1
Consumption Volume ventilation Rate residual capacity

Increase (up to Increase (up to Increase (Up to


Decrease Not Change Decrease (20%) Unchangeed
20%) 40%) 50%)
Receptor
Medula &
Pregnancy
Upregulated
Progesteron ↑ By Esterogen
Hipothalamus

Hiperemia &
Respiratory
Anatomical Center
Edema of
mucosa
Changes
Sensitivity Dilatation of
Respiratory
Growing Gravid of CO2 ↑ track
Uterus Diaphragm
Upward
Displacement Inspiratory &
Expiratory Maximum
Subcostal Angle
50%↑ Functional Pressure Values
Residual Remain Preserved
Capacity ↓
Pregnancy

Diaphragm Inspiratory
Tidal Volume ↑
Elevation Capacity ↑
50% (650 ml)
10%
Outward Recoil Of
The Chest ↓

Functional Residual Capacity


(FRC) ↓ 20-30%
Pregnancy

PaO2 ↑ 93-106 pH: 7,42-7,46 PaCO2 ↓ 37-30


mmHg mmHg

Respiratory
Alkalosis
URINARY TRACK SYSTEM
PHYSIOLOGY IN PREGNANCY
Pregnancy

Water & Sodium


eRPF GFR Glucosuria Proteinuria
Retention

Plasma
Increase (80%) Increase (50%) Osmolarity&
Sodium Decrease
Urinalysis using 24-h Glucosuria
H2O & K+
Pregnancy Urine Collection
Sample
Retention

Proteinuria
Plasma
Creatinine Level ↓ Osmolarity ↓
Average 0,4 mg/dl ≤ 300 md/dl 290 mOsm/kg -
Relaxin- (Physiologic) 280 mOsm/kg
mediated Nitric
Oxide Release ≥300 mg/dl
Glomerular (Abnormal)
Hyperfiltration Massive K+ ↓ to 136
mEq/L
Vasodilation

GFR↑ 50% Frequency & Urgency ↑


eRPF ↑ 80%
GASTRO INTESTINAL TRACK SYSTEM
PHYSIOLOGY IN PREGNANCY
Pregnancy

Lower Gastric Hepatic


Gastric
HCl pH Esophageal Emptying & Blood Flow
Secretion Motility ↑
Tone

pH Delayed ?? Hepatic
Increase Decrease
Decrease ? Enzyme ↑&↓

Effect of
Heartburn, Absorption of
Neausea, drug, e.g.
Vomitting (80%) Acetaminophen
Metabolism
Changes in phase 1 liver enzyme activity
• ↓CYP1A2 → clearance of caffeine,
olanzapine, clozapine ↓
• ↑CYP2D6 → clearance of fluoxetine ↑
• CYP2A6, 2C9, 3A4 ↑ → plasma
concentrations of drugs ↓ e.g. phenytoin,
midazolam

Changes in phase 2 liver enzyme activity


Uridine diphosphate glucuronosyltransferase
(UGT) 1 family
Changes
of several
drugs in
pregnancy
HAEMATOLOGY
PHYSIOLOGY IN PREGNANCY
Pregnancy

Coagulating Anticoagulan
Plasma Erythrocyte
Fibrinogen factor VIII, Erythropoiesis Platelet ts &
Volume life span
IX, X Fibrinolitic ↓

Increase Fall
Increase Increase Decrease Increase
Significantly Progressively
(50%) 2-10%
Woman: 100-
Plasma Volume 150 X109
↑Proportionally > cells/l
RBC mass

Physiological
Anemia
Physiology Of Lactation
• The breasts, begin to develop at puberty.

• stimulated by the estrogens stimulate growth


of the breasts’ mammary glands + the
deposition of fat to give the breasts mass.

• Progesterone is essential for the final


development of breasts into milk-secreting
organs, promoting growth of lobules and
development of secretory characteristics in
alveoli cells once the ductal system is
established.
• Estrogen and progesterone inhibit
milk secretion during pregnancy,
while prolactin promotes it.
• Prolactin, secreted by the anterior
pituitary gland, steadily increases
during pregnancy, peaking at birth.
• Colostrum, the fluid secreted before
and after birth, contains proteins and
lactose but minimal fat.
• After birth, the sudden decline in
estrogen and progesterone allows
prolactin to stimulate milk
production.
• Other hormones such as growth
hormone, cortisol, parathyroid
hormone, and insulin are also crucial
for milk formation.
• Nursing triggers surges in prolactin,
sustaining milk production, but
without continued nursing, milk
production ceases within a week.
EJECTION (OR “LET-DOWN”) PROCESS
IN MILK SECRETION

Milk is continuously secreted into the breasts' alveoli but


doesn't flow easily into the ducts until ejected.

Ejection is triggered by a neurogenic and hormonal reflex


involving oxytocin release from the posterior pituitary.

Initially, little to no milk is received by the baby, but suckling


stimulates oxytocin secretion.
EJECTION (OR “LET-DOWN”) PROCESS
IN MILK SECRETION

Oxytocin contracts myoepithelial cells, expressing milk into the ducts at


a pressure of +10 to 20 mm Hg.

Milk begins to flow within 30 seconds to 1 minute of suckling, a


process called milk ejection or let-down.

Suckling on one breast triggers milk flow in both breasts, and emotional
signals like fondling or hearing the baby cry can also stimulate milk
ejection.
Composition of Milk
• The concentration of lactose in human
milk is about 50% greater than in cow’s
milk, but the concentration of protein in
cow’s milk is ordinarily two or more times
greater than in human milk.
• At the height of lactation in the human
mother, 1.5 liters of milk may be formed
each day (and even more if the mother
has twins).
• Milk not only does milk provide the
newborn baby with needed nutrients, but
it also provides important protection
against infection.
The Onset Of Labour
• Parturition can be arbitrarily
divided into four overlapping
phases that correspond to the
major physiological transitions
of the myometrium and cervix
during pregnancy. These
include:
1. Prelude
2. Preparation
3. Process
4. Recovery
• Importantly, the phases
of parturition should not
be confused with the
clinical stages of labor.
1. The first stages of
labor
2. Second stages of labor
3. third stages of labor
make up phase 3 of
parturition
Myometrial Contractility
Cervical Dilatation
• The balance between myometrial relaxation and contraction is
controlled by steroid- and peptide-hormone transcriptional regulation
of key genes and their protein products
• To ensure uterine quiescence, the synthesis in the decidua of
prostaglandins, in particular PGF2α, is markedly suppressed.
Suppression of prostaglandin production here persists throughout
most of pregnancy, and suppression withdrawal is a prerequisite for
parturition
Actin-Myosin Interactions
• Uterine relaxation is sustained by
increasing myocyte cyclic adenosine
monophosphate (cAMP) levels.
• Elevated cAMP levels activate protein
kinase A (PKA).
• PKA promotes phosphodiesterase activity,
leading to dephosphorylation of myosin
light-chain kinase (MLCK).
• Other mechanisms maintain actin in a
globular form, preventing the formation of
fibrils necessary for contractions.
Actin-Myosin Interactions
• Uterine contractions occur when the
sequences are reversed.
• Actin transitions into a fibrillar form,
and calcium enters the cell, binding
with calmodulin to form complexes.
• These complexes activate myosin light-
chain kinase (MLCK), leading to the
phosphorylation of myosin light chains.
• Phosphorylated myosin generates
ATPase activity, initiating the sliding of
myosin over actin fibrils, resulting in
uterine contraction.
Phase 1
• In phase 1 of parturition, myeloid
and lymphoid immune cells (natural
killer cells, macrophages, dendritic
cells, and T cells) in collaboration
with decidual cells, promote an
environment of immune tolerance to
protect the fetus.
• Immune cells with innate and
adaptive immune responses support
vascular and tissue remodeling,
immune surveillance and defense,
and trophoblast invasion in phase 1
Cervical Softening
• The initial stage of cervical remodeling, known as softening,
commences during phase 1 of parturition.
• Softening involves increased tissue compliance, yet the cervix remains
firm and unyielding
• Palpable softening of the lower uterine segment at 4 to 6 weeks'
gestation, a sign historically used to diagnose pregnancy.
• Maintaining cervical anatomical and structural integrity is crucial for
pregnancy to progress to term clinically.
• Preterm cervical dilation or structural insufficiency may indicate
impending delivery.
Phase 2
• Progesterone withdrawal is associated
with parturition progression to labor
in certain species.
• Administering progesterone to the
mother can block the progression of
labor in species exhibiting
progesterone withdrawal.
• However, the effect of progesterone
administration in the absence of
classic progesterone withdrawal on
delaying the onset of labor or
preventing preterm labor is still
uncertain
• The amnion produces several bioactive peptides and prostaglandins
that can either relax or contract the myometrium.
• Towards the end of pregnancy, the synthesis of prostaglandins PGE2
and PGF2α in the amnion increases, with greater activity of
phospholipase A2 and PGHS-2.
• The amnion is the primary source of
prostaglandins found in amniotic fluid, and
they play a clear role in promoting
membrane rupture.
• However, the impact of amnion-derived
prostaglandins on uterine quiescence and
activation is less understood due to limited
access to maternal tissues caused by the
expression of PGDH.
Phase 2
• Phase 2 changes in the myometrium
prepare it for labor contractions.
Changes result from a shift in the
expression of proteins that control
uterine quiescence to an
expression of CAPs
• Another critical change in phase 2 is
formation of the lower uterine
segment from the isthmus. With this
development, the fetal head often
descends to or even through the
pelvic inlet lightening. The
abdomen commonly undergoes a
shape change
• The first stage begins when
spaced uterine contractions
of sufficient frequency,
intensity, and duration are
attained to bring about cervical
thinning, termed effacement.
• The interval between
contractions narrows gradually
from approximately 10
minutes at the onset of first-
stage labor to as little as 1
minute or less in the second
stage
• The upper segment is firm during contractions,
whereas the lower segment is softer, distended, and
more passive.
• This mechanism is imperative because if the entire
myometrium, including the lower uterine segment
and cervix, were to contract simultaneously and
with equal intensity, the net expulsive force would
markedly decline.
• Thus, the upper segment contracts, retracts, and
expels the fetus.
• In response to these contractions, the softened lower
uterine segment and cervix dilate and thereby form
a greatly expanded, thinned-out tube through
which the fetus can pass.
• Schematic showing effacement and
dilation.
A. Before labor, the primigravid cervix
is long and undilated in contrast to
that of the multipara, which has
dilation of the internal and external
os.
B. As effacement begins, the multiparous
cervix shows more dilation and
funneling of the internal os
compared with the primigravid cervix.
C. As complete effacement is achieved in
the primigravid cervix, dilation is
minimal.
The reverse is true in the multipara.
Uterine Involution
After delivery, Uterine blood flow gradually diminishes
to approximately that of the prepregnant state. Within
the puerperal uterus, larger blood vessels become
obliterated by hyaline changes. They are gradually
resorbed and replaced by smaller ones. Minor vestiges
of the larger vessels, however, may persist for years.
• During labor and vaginal delivery, the margin of the dilated cervix, which corresponds
to the external os, may be lacerated.
• The cervical opening contracts slowly, and for a few days immediately after labor, it
readily admits two fingers.
• parous cervix in the end of the first week characterize narrow opening, the cervix
thickens, and the endocervical canal reforms. The external os does not completely
resume its pregravid appearance. It remains somewhat wider, and typically,
ectocervical depressions at the site of lacerations become permanent.
• Cervical epithelium also undergoes considerable remodeling. This actually may be
salutary because almost half of women have regression of high-grade dysplasia
following delivery
Phase 4
• Immediately and for about an hour after
delivery, the myometrium remains
persistently contracted.
• This directly compresses large uterine vessels
and allows thrombosis of their lumens to
prevent hem
• Uterine involution and cervical repair are
prompt remodeling processes that restore
these organs to the nonpregnant state.
• These protect the reproductive tract from
invasion by commensal microorganisms and
restore endometrial responsiveness to
normal hormonal cyclicity hemorrhage.
CONCLUSION
Reference
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