Maternal physiology

Maternal physiology
During
Duringpregnancy
pregnancy
INTRODUCTION
The pregnant woman undergoes profound anatomic
and physiologic changes in almost every organ system.
These adaptations to the pregnant state begin just after
conception and evolve through delivery, after which
they almost completely revert back to the nonpregnant
state over a period of weeks. The purpose of these
alterations is to accommodate the needs of the
maternal-fetal unit.
 Objectives for learning:

 Review some of the physiological changes in pregnancy: For example:

 CO is ↑ in pregnant women, but smooth muscle (e.g., urinary and gastrointestinal

tracts) demonstrates ↓ activity.

 Many laboratory values are dramatically altered form non pregnant values.

 physiological adaptations of normal pregnancy can be misinterpreted as

pathological but can also unmask or worsen preexisting disease.

 An understanding of the normal physiologic standing coincidental disease processes.

 Review case presentations for some medical and surgical conditions that occur
during pregnancy
 Maternal physiology
Maternal physiology
During pregnancy
During pregnancy

Definition:
 Is an extensive physiologic, biochemical, and

anatomic changes that occur during pregnancy,

and may be systemic or local. However, most
systems return, to pre-pregnancy status within 6
weeks postpartum. These physiologic changes called
also maternal adaptations.
 Maternal physiological changes in pregnancy are
the normal adaptations that a woman undergoes
during pregnancy to better accommodate the
embryo or fetus.

 Maternal adaptations maintain a healthy

environment for the fetus without compromising
the mother’s health
 Maternal physiology are largely secondary to the effects
of progesterone and estrogen, begin as early as 4 weeks
gestation and are progressive. In the first 12 weeks of
pregnancy progesterone and estrogen are produced
predominately by the ovary and thereafter by the
placenta. These changes both enable the fetus and
placenta to grow and prepare the mother and baby for
childbirth.
 After conception, the corpus luteum, placenta,
and developing embryo release hormones,
growth factors, and other substances into the
maternal circulation. These substances trigger a
cascade of events that transform the
functioning of the maternal cardiovascular,
respiratory, and renal systems, which in turn
alter the physicochemical determinants of
[H(+)].
Following implantation, maternal adaptations accomplish three
important functions that support fetal growth.
1. Increased availability of substrates and precursors for
fetal-placental metabolism: hormone production is mediated
by increases in dietary intake, as well as endocrine changes
that increase the availability of glucose and low-density
lipoprotein (LDL) cholesterol.
2. Transport capacity is enhanced by increases in CO,
facilitating the transport of substrates and precursors to the
placenta, and fetal waste products to maternal organs for
disposal.
3. Disposal of additional waste products (heat, CO2 , and
metabolic products) occurs through peripheral
vasodilatation and increases in skin blood flow, ventilation,
and renal filtration.
 PHYSIOLOGICAL ADAPTATIONS TO
PREGNANCY

 Numerous normal changes in response to pregnancy

 Itis important to have an awareness of what is considered “normal”

in pregnancy

 Such awareness allows an obstetrician to diagnose and manage

common problems such as
 Hypertension
 Hyperthyroidism
 Anemia
 Asthma
 Diabetes
 Seizure disorders
 Urinary Tract Infections/ Acute Pyelonephritis
 SYSTEMIC CHANGES
A. Volume homeostasis
B. Gastrointestinal tract
C. Kidneys and urinary tract
D. Hematologic system
E. Cardiovascular system
F. Pulmonary system
G. Metabolism
H. Endocrine
I. Musculoskeletal and dermatologic
 Volume homeostasis changes
1. One of the most fundamental systemic changes of a
normal pregnancy is fluid retention.

2. weight gain of 11-13kg.

3. There is some increase in intracellular water, but the most

marked expansion occurs in extracellular fluid volume,
especially circulating plasma volume.

4. There is a net retention of sodium during pregnancy,

amounting to a total of 900 mmol (or 3—4 mmol per day).
 Volume homeostasis
a. fluid retention: which accounts for between 8 and 10kg of the average
maternal weight gain of 11-13kg.
a. Some increase in intracellular water
b. most marked expansion occurs in extracellular fluid volume,
especially circulating plasma.

 increases output and in renal blood flow

b. PV increase
 significantly in women taking regular exercise during pregnancy,
and
 relatively smaller increases occur in the pregnancy complications of
:
 intrauterine growth restriction (IUGR) and pre-eclampsia.
The factors contributing to fluid retention are:

a) Sodium retention: amounting to a total of 900 mmol (or

3—4 mmol per day).
b) Resetting of osmostat: plasma osmolality ↓ by
about 10 mosmol/kg.
c) Decrease in thirst threshold
d) Decrease in plasma oncotic pressure.
The consequences of fluid retention are:

a) Hemoglobin concentration falls

b) Hematocrit falls.
c) Serum albumin concentration falls.
d) Stroke volume increases.
e) Renal blood flow increases.
 Weight Gain in Pregnancy
1. Normal weight gain can be 30-35 lbs in average patient and
50-70 lbs. in twin pregnancy

2. Daily requirements of 2000-2500 calories

3. Associated with good outcome, i.e. delivery of normal sized

baby

4. Excess weight gain associated with variety of complications:

 GDM, pre-eclampsia, macrosomia

5. Total pregnancy expenditure is 75,000kcalories

6. Recommendations for appropriate weight gain in pregnancy

based on initial weight, BMI
 Weight increase
 There is an increase weight of approximately 12.5 Kg at
term
 The main increase occurs in the 2nd half of the pregnancy,
0.5 Kg/week

 Causes:
 growth of the conceptus
 enlargement of the maternal organs
 maternal storage of fat
 increase in maternal blood and interstitial fluid
 Weight Gain in Pregnancy
Kg. Lbs.
Thin
(BMI <19.8) 12.5-18 28-40

Average
(BMI 19.8-26.0) 11.5-16 25-35

Heavy
(BMI 26.1-29.0) 6.0-11.5 15-25

Obese
(BMI > 29.0 6.0 15
Edema

 Edema, or swelling, of the feet is common during

pregnancy, partly because the enlarging uterus
compresses veins and lymphatic drainage from the
legs.
 Gastrointestinal Changes
 Key Changes
 Appetite Usually increased, with cravings
 Gastric Reflux Sphincter relaxation
 GI Motility Decreased
 GI Transit Time Slower
 Liver Functionally unchanged
 Gallbladder Dilated
GASTROINSTESTINAL TRACT

1.Oral cavity:
 Salivation: increase due to swallowing
difficulty associated with nausea.

 hypertrophic and hyperaemic of the gums:

often become spongy and friable with bleed
easily. This may be due to increased systemic
oestrogen.  
GASTROINSTESTINAL TRACT
2. Gastrointestinal Motility reduced:

Gastric motility ↓and empty time ↑ from the progesterone

effect on smooth muscles.→ increase in stomach residual
volume, along with upward displacement of intra-abdominal
contents by the gravid uterus predisposes to aspiration.

Large bowl colonic motility ↓ and transient time ↑ from

the progesterone effect on smooth muscles. This predisposes
to increase colonic fluid absorption resulting in constipation.
 Gastrointestinal tract

a. Nausea and Vomiting (morning sickness); which may be due to

elevated B-hCG and should resolve by 14 to 16 weeks
 Exact etiology is unknown
 Supportive therapy usually helpful
 On rare occasion, TPN and hyper-alimentation necessary

 Dietary cravings commonplace

 Pica
 Ptyalism
 Gastrointestinal tract

b. prolonged gastric empty time, decreased gastro-esophageal

sphincter tone, which can lead to acid-reflux→ heartburn
c. acid reflux secondary to decreased gastroesophageal
sphincter tone.
d. decreased colonic motility, which leads to increased water
absorption and constipation.
e. Gastric hydrochloric acid production is variable, usually is
reduced. but sometimes is exaggerated, especially first
trimester → heartburn .
f. Gastrin hormone productions increase significantly, resulting
increased stomach volume and decreased stomach pH.
 GASTROINSTESTINAL TRACT
GASTROINSTESTINAL TRACT
GASTROINTESTINAL TRACT
GASTROINTESTINAL TRACT

g) Gastric production of mucus may be increased. heartburn

g) Gastric production of mucus may be increased. heartburn
h) Oesophageal peristalsis is decreased → ↑gastric reflux because of the slower emptying
h) Oesophageal peristalsis is decreased → ↑gastric reflux because of the slower emptying
time and dilatation or relaxation of the cardiac sphincter. ↑gastric reflux→ heartburn
time and dilatation or relaxation of the cardiac sphincter. ↑gastric reflux→ heartburn

i) Gastric reflux is more prevalent in later pregnancy due to elevation of the stomach
i) Gastric reflux is more prevalent in later pregnancy due to elevation of the stomach
(cardiac sphincter) by the enlarged uterus. heartburn
(cardiac sphincter) by the enlarged uterus. heartburn

j) increased stomach acidity, slower emptying time, and increased intra-gastric pressure
j) increased stomach acidity, slower emptying time, and increased intra-gastric pressure
caused by the enlarged uterus), as well as lying supine, make the use of anaesthesia more
caused by the enlarged uterus), as well as lying supine, make the use of anaesthesia more
hazardous because of the increased possibility of regurgitation and aspirations.
hazardous because of the increased possibility of regurgitation and aspirations.
regurgitation and aspirations
regurgitation and aspirations
 GASTROINSTESTINAL
GASTROINSTESTINALTRACT
TRACT
SMALL & LARGE BOWEL & APPENDIX
SMALL & LARGE BOWEL & APPENDIX
As the uterus grows and the stomach is pushed upward, most parts of the large
As the uterus grows and the stomach is pushed upward, most parts of the large
and small bowel move upward and laterally.
and small bowel move upward and laterally.

GALLBLADDER  
GALLBLADDER  
a.Gallbladder function is also altered during pregnancy because of hypotonic of
a.Gallbladder function is also altered during pregnancy because of hypotonic of
the smooth muscle wall.
the smooth muscle wall.
b.Emptying time is slowed and emptying often incomplete.
b.Emptying time is slowed and emptying often incomplete.
c.the gallbladder often appears dilated and atomic.
c.the gallbladder often appears dilated and atomic.
d. Bile can because thick and bile stasis may lead to gallstone formation.
d. Bile can because thick and bile stasis may lead to gallstone formation.
e.Increased tendency for gallbladder dysfunction with possible need for surgery,
e.Increased tendency for gallbladder dysfunction with possible need for surgery,
or laparoscopic cholecystectomy
or laparoscopic cholecystectomy
f. The chemical composition of bile is not appreciable altered.
f. The chemical composition of bile is not appreciable altered.
g.Plasma cholinesterase activity is decreased during normal pregnancy
g.Plasma cholinesterase activity is decreased during normal pregnancy
 
 GASTROINSTESTINAL
GASTROINSTESTINALTRACT
TRACT
LEVER  
LEVER  
no apparent morphologic changes in the liver during normal
no apparent morphologic changes in the liver during normal
pregnancy, but there are functional alterations.
pregnancy, but there are functional alterations.

Serum alkaline phosphatise activity can double, probably because

Serum alkaline phosphatise activity can double, probably because
of increase placental alkaline phosphates.
of increase placental alkaline phosphates.

decrease in plasma albumin and a slight decrease in plasma

decrease in plasma albumin and a slight decrease in plasma
globulins.
globulins.
In non-pregnant patients, such a decrease could be an indication
In non-pregnant patients, such a decrease could be an indication
of liver.
of liver.
 Hepatic Function Laboratory Studies

Albumin 20% decrease

Total Protein Slight decrease
Alkaline Phosphatase Markedly elevated
Bilirubin Unchanged
PT/PTT Essentially unchanged
Clotting Factors General increase at term
Triglycerides Gradual increase at term
Cholesterol Twice normal value
GASTROINSTESTINAL TRACT

a) nausea and vomiting

b) acid-reflux
c) constipation.  
d) heartburn.
e) regurgitation and aspirations.
f) gallstone formation.
g) ↑ Serum alkaline phosphatise activity can double,
probably because of increase placental alkaline
phosphates.
h) ↓ plasma albumin and a slight decrease in plasma
globulins.
 Cardiovascular

 Estrogen and progesterone mediated relaxation of vascular

smooth muscle in pregnancy cause vasodilatation reducing
the peripheral vascular resistance by 20%.

 Consequently systolic and diastolic blood pressures fall.

 A reflex increase in heart rate by 25% together with a 25%

increase in stroke volume, results in a 50% increase in
cardiac output.
 During labour cardiac output may increase further by up to
45%.
 Cardiac contractility remains unchanged.
 The rise in cardiac output is facilitated by anatomical
changes, namely left ventricular hypertrophy and dilatation.
 Estrogen and progesterone
relaxation of vascular smooth
muscle

↓ the peripheral vascular resistance by 20%.

Vasodilatation

systolic and diastolic blood pressures fall.

A reflex

↑in HR by 25% and ↑ in stroke volume 25%

↑in cardiac output.50%

left ventricular hypertrophy and dilatation

 CARDIOVASCULAR SYSTEM

1. Heart rate increase (15 beats/min more than usual)

2. stroke volume increases 25—30% reaching its maximum at

12—24weeks’ gestation.

3. Cardiac output increases by about 30-50%, mostly during

the first trimester, with the maximum being reached between
20 and 24 weeks gestation and maintained during pregnancy.

N.B: The increase is mainly due to an increase in plasma volume

through increased aldosterone.
 CO is the product of heart rate (HR) and stroke volume
(SV), and both increase in pregnancy.
CO= HR x SV

 Heart rate increase by 20 beats/min by third trimester

 SV increase by 30% by the end of the first trimester.

Increased Cardiac Output
CARDIAC OUTPUT DURING
PREGNANCY
 CO depend on maternal position:

1. CO is lowest in supine position because of the

inferior vena cave compression resulting decreased
cardiac return follow-on in a decrease of cardiac
output, maternal blood pressure and placental
perfusion.

2. CO is the highest in the left later position.

3. CO increases progressively through the three stages

of labor
Decreased Stroke Volume
 The descending aorta can also be compressed by the
uterus causing a reduction in uterine blood flow.
Aortocaval compression must be considered as a
cause of maternal hypotension from the end of the
1st trimester onwards, though it typically occurs
after 20 weeks gestation.
 The maternal compensatory mechanism for
aortocaval compression comprises of an increase in
sympathetic tone causing vasoconstriction and
tachycardia and diversion of blood flow from the
lower limbs through the vertebral plexus and the
azygos veins to reach the right heart.
 In 10% of parturients this is inadequate to maintain
blood pressure in the supine position and
hypotension may be severe enough for the mother
to lose consciousness.

 Obstetricians and anesthetists should be aware that

fetal hypoxia due to aortocaval compression may
occur in the asymptomatic mother.
 Intravenous and inhalational anesthetic agents,
causing a reduction in stroke volume and cardiac
output, and neuroaxial blockade (spinal/epidural),
causing sympathetic blockade, increase the risk of
supine hypotension. Whenever possible pregnant
patients should adopt a full lateral position. When
supine position is required they should be tilted to
the left or have a wedge inserted under their right
hip.
 Heart rhythms & murmurs

 Systolic ejection murmur along the left sternal

border is normal in pregnancy owing to increased
CO passing through aortic and pulmonary valves.

 Diastolic murmurs are never normal in pregnancy

and must be investigated.
 Cardiac Changes in Pregnancy
 Cardiac output increases around 50% from an increase in
HR and SV (3L/min to 6.2L/min)

 There is an additional 40% increase above that level

during active labor

 Immediately following delivery, cardiac output may be

increased by an additional 10-20%

 Cardiac exam is different during pregnancy

 Many patients will have an S3 after mid-pregnancy
 Diastolic murmurs are usually considered serious
 Systolic murmurs (“flow murmurs”) common
 Displacement of heart is to right and upwards
 EKG shows left axis deviation and low voltage QRS complexes
 Key Cardiovascular Changes During Pregnancy
Blood Flow to Other Organs Increased
Peripheral Vascular Resistance Decreased

Blood Pressure Mid pregnancy decrease

Pulmonary Blood Pressure Unchanged

Heart Size Increased
Cardiac output Increased
Stroke volume Increased
Systolic murmurs Common
Diastolic murmurs Potentially pathological

EKG changes LAD, low voltage

4. The systemic vascular resistance decreases due to the smooth
muscle relaxation and overall vasodilatation caused by elevated
progesterone, resulting in a fall in arterial blood pressure.

PVR= BP/CO declines 30%

because BP decreases and CO increases, PVR declines 30%, reaching

its nadir by 20 weeks . This enhances uteroplacental perfusion.

a. ↓ systolic blood pressure of 5-15 mm Hg

b. ↓ diastolic blood pressure of 10-15 mm Hg that nadirs at 24 weeks.

c. Between 24 weeks gestation and term, blood pressure slowly returns to

prepregnancy levels but should never exceed them.
Venous blood pressure –Central venous pressure
(CVP) is unchanged with pregnancy, but femoral
venous pressure (FVP) is increased two -to threefold
by 30’weeks gestation
Circulatory Changes in Pregnancy
Hemodynamic Changes During Labor
More Hemodynamic Changes
 RISPIRATORY CHANGE
Key words
 TLC—Total lung capacity

 VC—Vital capacity

 IC— Inspiratory capacity

 FRC—Functional residual capacity

 IR—inspiratory reserve volume

 TV—Tidal volume

 ERV—Expiratory reserve volume

 RV— residudal volume.

 Pulmonary Adaptations
 Anatomical
 Increased chest diameter, subcostal angle changes,
increased diaphragmatic excursion with diaphragm
elevated as well
 Physiological
 Hyperventilation,
 Increased IC,VC and Minute Volume,
 Residual volume decreased,
 Expiratory Reserve Volume decreased,
 Tidal volume increased by 40%,
 pO2 increased,
 pCO2 decreased,
 arterial pH unchanged, and serum bicarbonate reduced
 PULMONARY
 Tidal volume (TV) is the volume of air that moves in
and out of the lungs at the rest.
 VT Increases with the pregnancy to 30-40%, from 0.45
to 0.65 litres
 Minute ventilation (VF) is increase up to 40% with the
major increase by 20 weeks.
 Residual volume(VR) is decreases up to 20% by the
third trimester.
 Blood gases: the rise in VT produces a respiratory
alkalosis with a decrease in PCO2 from 40 to 35mm Hg
and increase in PH from 7.40—7.45.
Pulmonary Changes in
Pregnancy
Respiratory Changes in Pregnancy
 Kidneys and urinary tract
 The kidneys actually increase in size and the ureters dilate during
pregnancy , owing to the progesterone effect on the smooth
muscle which may lead to increased rates of pyelonephritis. the
right side dilates more than the left in 90% of patients.

 The glomerular filtration rate (GFR) increased by 50% early in

pregnancy and is maintained until delivery.
As result of increased GFR, blood urea nitrogen (BUN),
creatinine, and uric acid. decreased by about 25%.

 Glucosuria, urine glucose normally increases. Glucose is freely

filtrated and actively reabsorbed. However, the tubular
reabsorption threshold falls from 195 to155 mg/dl

 Proteinuria, urine protein is unchanged.

 The renin-angiotensin system is increased, and
causing increased aldosterone levels.

 High level of aldosterone results in increased

sodium reapsorpation; however, plasma levels of
sodium do not increase because of the simultaneous
increase of GFR
 Renal Changes in Pregnancy
 Minimal renal enlargement, bilaterally
 Both renal pelvises and ureters are dilated
(“hydronephrosis of pregnancy”)
 Greater urinary stasis, ureteral compression,
leading to urinary stasis and possilbe urinary tract
infections, pyelonephritis
 Loss of urinary control
 Bladder capacity diminished
 RPF increases to 75% of non-pregnant value
 More Renal Changes in Pregnancy

 GFR increases 50% over non-pregnant state

 Creatinine clearance increases to 150-200 ml/min
 Plasma osmolality decreases
 Urine output is unchanged
 There is an increased sensitivity to renin and
angiotensin
 Renal glycosuria common
 Proteinuria up to 300 mg/24 hours normal
 HEMATOLOGIC SYSTEM

1. the plasma volume increases by 50%

2. ↑blood volume by 50% with significant increase by

the first trimester maximum increase is by 30
weeks (multiple fetuses)

3. Red cell mass, white cell count and platelet

production are all increased during pregnancy.
 Normal Changes in Pregnancy
 Blood volume gradually increases to:
 Meet the increased needs of the fetus
 Allow for adequate perfusion of the uterus
 Prepare for the blood loss during childbirth
 Number of red blood cells will increase
 The patient is able to clot faster.
 The patient’s heart rate increases up to 20%.
 plasma volume

 Increased concentrations of progesterone and estrogen

directly act on the kidney causing the release of renin.
This activates the aldosterone-renin-angiotensin
mechanism leading to renal sodium retention and an
increase in total body water. Plasma volume increases by
45% and as this increase is relatively greater than the
increase in red cell mass, maternal hemoglobin
concentrations falls from 150 g per liter pre-pregnancy to
120 g per liter during the 3rd trimester
 This is termed physiological anemia of pregnancy.
Increased Blood Volume
DILUTIONAL ANEMIA OF
PREGNANCY
 Red blood cells
 Renal erythropoietin production increases leading to
a 20% increase in red cell mass.

 the red blood cell volume increases only by 20-30%.

1. Oxygen carrying-capacity increases

2. the hematocrit decreases on lab value; this is not a

true decrease in hematocrit, however, but rather due
to the dilution.
Hematological Changes in Pregnancy
 Plasma volume increases early in pregnancy with a 50% increase
(and higher in higher order multiple pregnancies) and a delayed
increase in RBC mass and volume but less than the plasma volume

 Normal pregnancy associated with a “demand” of 1000 milligrams

of additional iron
 500 mg. to increase maternal RBC volume
 300 mg. transported to fetus
 200 mg. for normal iron loss

 60 mg. of elemental iron required daily, provided in 300 mg. of

ferrous sulfate

 Serum iron decreased

 Transferrin and TIBC are increased .

 Iron
Metabolism
in
Pregnancy
 White blood cell count
 The white blood cell count (WBC), count increases
progressively during pregnancy with a mean value of
up to 16,000/m3 in the third trimester.

 N.B: The WBC increases to a mean of 10.5 million/mL,

with a range to 6 to 16 and may peak at over 20 mg/mL
stressful conditions (during labor).

 The rising white cell count during pregnancy, which

peaks after delivery, can make diagnosis of infection
difficult.
 Platelet count
platelet count normal reference range is unchanged in pregnancy.

Platelet production is increased, but platelet consumption increases

more, causing the platelet count to fall to low normal values.

there is a slight decrease in platelet concentration to a minimal

normal values of 100-150 mil/mL. secondary to increase plasma
volume and an increased in peripheral destruction.

N.B: a drop in the platelet count below 100 million/mL or over a

short time period is not normal and should be investigated.
6. Coagulation factors: factors VII, VIII,IX, and X increase
progressively in pregnancy, leading to a hypercoagulable
state.
7. A pregnancy is considered to be hypercoagulable state,
leading to increased risk for developing blood clots and
embolisms, due to increased liver production of coagulation
factors, mainly fibrinogen and factor VIII (this
hypercoagulable state along with the decreased ambulation
causes an increased risk of both DVT and PE).

7. The actual clotting and bleeding times do not change.

8. The increased rate of thromboembolic events in pregnancy

may be secondary to an increase in venous stasis and vessel
endothelial damage.
 More Hematological Changes
Occurring During Pregnancy
 Pregnancy considered a “hypercoagulable state”
 Fibrinogen increases to 450-600 mg/dl
 Factors VII, VIII, IX and X increase
 Prothrombin, Factor V, and XII are unchanged
 Bleeding time does not change
 Platelet count may increase to 450,000 to 600,000

 WBC count may increase to as high as 20,000 due

to an increase in granulocytes
 Reproductive Tract or Genital
changes
Uterus
The body of the uterus:
 Height and weight (hyperplasia)
the height increases from 7.5 cm to 35cm
the weight increases from 50g to 1000g at term
 Uterine ligaments show hypertrophy
 Dextro -rotation: the uterus is tilted and twisted to
the right in 80% of cases
 Lower uterine segment (LUS): the LUS is formed
from the isthmus from the 4th month to reach 10
cm at full term.
 Genital changes
The cervix :
 edema and congestion, and becomes soft

 mucus plug (operculum):

cervical mucus closing the cervical canal

 increased secretion from its glands

The vulva:
shows increased vascularity and varicosities
 Genital changes
The vagina:
 shows increased vascularity soft, moist & bluish
 distention of vagina at birth

The ovary
 shows increased vascularity and size

 one ovary contains the corpus luteum

Pelvic ligaments:
 relaxation of the ligaments

 relaxation of the pelvic joints

 the pelvis become more mobile and increases in capacity

 Breast changes

 Increased size and vascularity warm, tense &tender

 Increased pigmentation of the nipple and areola
 Secondary areola appear (light pigmentation around the 1ry
areola)
 Montgomery tubercules appear on the areola (dilated
sebaceous glands)
 Colostrum like fluid is expressed at the end of the 3rd month
ENDOCRINE
ENDOCRINECHANGES
CHANGESDURING
DURING
PREGNANCY
PREGNANCY
Pregnant women experience adjustments in their
endocrine system.
The most important endocrine changes are the
production of:
1. Human chorionic gonadotropin (β-hCG)
2. Human placental lactogen (hPL)
3. Prolactin
4. progesterone and estrogen by the placenta.
Maternal hormone levels, which differ from those in the
nonpregnant state, are dependent on:

a. The presence of a placenta (a rich store of steroid and

protein hormones)

b. The presence of a fetus:

in the ♂ fetus the testes, in response to βhCG,
produce testosterone, which is necessary for normal
male development.
In the ♀ fetus, normal development is not depend
on fetal ovarian steroid production

c. The presence of elevated levels of circulating estrogens

d. The ability of the placenta to regulate molecular
transport by permitting or restricting passage and
transfer of oxygen and nutrient from the mother to
the fetus and metabolic wastes and carbon dioxide
from the fetus to the mother.
Estrogens have the following affects:

1. They increase the effects of binding protein such

TBG, and CBG.

2. They partially inhibit the enzyme 3- β-

hydroxysteroid dehydrogenase.

3. They inhibit maternal pituitary gonadotropin

synthesis and release, thus making placental
gonadotropins responsible for gonadtropic
function.
FOUR
FOURCHARACTERS
CHARACTERS..
1. Chemical nature

2. Source

3. Normal patterns

4. Significance
 II. HUMAN CHORIONC GONADOTROPIN (hCG)

A. Chemical nature. Is a glycoprotein with molecular

weight of approximately 35,000 and composed of two
dissimilar side chains. The α and β subunits.

1. The α-subunit is biochemically similar to Alfa subunit:

a. Luteinizing hormone (LH)

b. Follicle-stimulating hormone (FSH)

c. Thyroid-stimulating hormone (TSH)

2. The β-subunit is relatively unique or specific to hCG.

B. Source. It is produced by placental syncytiotrophoblast. hCG
is produced by trophoblastic tissue in the following conditions.

1) Normal placenta tissue as early as 6 to 8 days

2) postconception as shown by immunofluoresence.

3) Multiple placental development (multiple gestation)

4) Hydatidiform moles by virtue of trophoblast proliferation

5) Choriocarcinoma cells

6) Ectopic pregnancy.
C. Mode of determination. hCG levels can be measured by
biological and immunological assays and Radioreceptor
assays on blood or urine.

D. Normal patterns.
 hCG rises rapidly 8 days postconception and first

appearing in the maternal blood 10 days after

fertilization.
 doubling every 2 to 3 days and reaching a peak at
approximately 80 days (10 to 12 weeks),
 Dropping to a plateau after 15 weeks at (20-22 wks) and
reaching a steady state for the remainder of pregnancy.
 hCG is detectable throughout pregnancy.
 E. Significance.

a. Maintain corpus luteum production of

progesterone until the placenta can take over
maintenance of pregnancy.

b. Regulate steroid biosynthesis in the placenta and

adrenal glands as well.

c. Stimulate testosterone production in the male tests

(leydig cells )
hCG determinations are used as :
1. a marker for pregnancy (pregnancy testing)

1. inadequate level early in pregnancy suggest poor placental

function and may predict:
a. ectopic pregnancy
b. threatened abortion or
c. missed abortion.

2. Excessive level suggest:

a) multiple gestation or
b) trophoblastic neoplasia. (e.g. hydatidiform mole and
Choriocarcinoma), and embryonal carcinoma.
 hCG determinations are used as :

2. to follow the course of patients treated for

trophoblastic neoplasia.

3. hCG is used clinically for induction of ovulation

to treat anovulation based on its biological
stimulating to that of LH
 HUMAN PLACENTAL
LACTOGEN (hPL)
A. Chemical nature. hPL is a protein hormone with
growth hormone and Prolactin-like effects. its molecular
weight is 22,000

B. Source and Normal patterns. hPL is formed by the

syncytiotrophoblast as early as 3 weeks postconception
and can be detected in maternal serum as early as 6
weeks postconception, and disappears promptly from
the blood after delivery. It has a half-life of
approximately 15 minutes.
Pregnancy change—its level parallels
placental growth, rising throughout the pregnancy.
C. Mode of determination. hPL is measured by
radioimmunoassay.

D. Significance
 It induces lipolysis and elevates plasma free fatty acids,

which provide energy for the mother, conserving blood

glucose for use by the fetus.
 It induces insulin resistance and carbohydrate intolerance in

the mother (it decrease maternal tissue sensitivity to insulin

resulting in gestational diabetes )
 It inhibits glucose uptake and gluconeogenesis in the mother.

 It has an insulinogenic action, which elevates plasma insulin

level, favouring protein synthesis and ensuring a source of

amino acid for fetus.
Effect: It antagonizes the cellular action of insulin,
decreasing insulin utilisation , thereby contributing to
the predisposition of pregnancy to glucose intolerance
and diabetes.

hPL determinations have been used to test placenta function;

however, fetal heart rate monitoring techniques are more
reliable and sensitive in assessing fetal well-being.

If levels are low :

Threatened abortion
Intrauterine growth retardation (IUGR)
 VI. PROGESTERONE
A. chemical nature. Progesterone is ∆-4,3ketosteroid
hormone that contains 21 carbon atoms. It has two
angular methyl groups at the 10 and 13 positions and a
two carbon side chain at the 17 position.

B. Source.
In the nonpregnant state, progesterone is produced
by all steroid forming glands, including the ovaries, testes,
and adrenal cortex. It serves as an
intermediary and precursor for other hormones (e.g.
testosterone, corticosteroids, and 17-hydooxyl
progesterone) and as an end- product when it is produced
by the corpus luteum.
 In the pregnant state, progesterone has a dual source:
a. it is produced exclusively by the corpus luteum up to the
6-7 wks of pregnancy.

b. Between 7 and 9 both, corpus luteum and placenta

produce progesterone

c. after 9 wks the corpus luteum declines and progesterone

production is exclusively by placenta.

 This point is clinically significant because progesterone

produced by the corpus luteum is essential for pregnancy
maintenance until the eight week.
C. Mode of determination.
 Progesterone can be measured in the blood by

radioimmunoassay and competitive protein binding

assay.

 Some laboratories may measure pregnanediol, the

major metabolite of progesterone, by 24- hour
analysis
 Normal patterns
 In a nonconception cycle, the progesterone peak
reaches 25 mg/day, and levels measure approximately
20 to 25 ng/ml in peripheral blood.

 the placenta produce 250 mg/day; most of the

progesterone produced enters the maternal circulation.
 A transient decline in peripheral blood progesterone
levels has been described in the 7 to 8wks of
pregnancy, the time of the luteoplacental shift;
however, the subtle change can be appreciated only
when daily measurements are made.
D. Significance.
Progesterone has all of the following properties:

1. In early pregnancy it induces endometrial secretory changes

favourable for blastocyte implantation and it maintains the
endometrium

2. In later pregnancy its function is the induce immune tolerance

for the pregnancy and prevent myometrial contraction (relaxes the
myometrium)

3. It has natriuretic actions and, thus, stimulates the increased

production of aldosterone during pregnancy.

4. It serves as a major precursor for critical fetal hormones during

pregnancy.
  
IV. ESTROGENS

A. Definition:
There are steroid hormones, which occur in three forms,
each of unique significance during a woman’s life :

1)Estradiol

2)Estriol

3)Estrone
 Estradiol, the most potent estrogen and
predominant moiety during the nonpregnant
reproductive years. It contains two hydroxyl groups
at the 3 position 3 and 17.

 It is converted from androgens (produced from

cholesterol in the follicular theca cells ), which
diffuse into the glandulous cell containing the
Aromatase enzyme that completes the
transformation into estradiol.
 2. Estriol : Is the mean estrogen during pregnancy, and
accounts for 90% of the estrogens produced during
pregnancy.

Dehydroepiandrosterone-sulfate (DHEA-S) from the

fetal adrenal gland is precursor for 90% of estriol
converted by sulfates enzyme in the placenta.

3.Estrone Is the mean from during menopause.

Postmenopausal adrenal androstenedione is converted in
peripheral adipose tissue to estrone.
 Endocrine Changes with Pregnancy
 Carbohydrate Metabolism
 Overall effect is that pregnancy is diabetogenic
 First half: tendency to hypoglycemia
 Second half: tendency to hyperglycemia
 Progressive insulin resistance as pregnancy
progresses
 Progesterone
 Estrogen
 HPL
 “Typical” FBS less than in non-pregnant state
 Blunting response to meals, eating as pregnancy
progresses
 Hypertrophy of beta cells as well
Diurnal Glucose and Insulin
Changes in Late Pregnancy
 Thyroid Physiology
 The maternal thyroid gland undergoes a number of
physiologic modifications to meet the metabolic
demands of pregnancy.

  The diagnosis of thyroid disease during pregnancy

requires an understanding of the changes in thyroid
physiology and thyroid function tests that accompany
normal pregnancy.

 To meet the increased metabolic needs during a normal

pregnancy, there are changes in thyroid physiology that
are reflected in altered thyroid function tests :
 Thyroid physiology 
 The major changes in thyroid function during pregnancy are:
1. an increase in serum thyroxine-binding globulin (TBG) concentrations
and

2. an increase in stimulation of the thyrotropin (TSH) receptor by human

chorionic gonadotropin (hCG).

N.B: hCG is one of a family of glycoprotein hormones, including TSH, with a

common alpha-subunit and a unique beta- subunit. However, there is
considerable homology between the beta-subunits of hCG and TSH. As a
result, hCG has weak thyroid-stimulating activity .

In a human thyroid cell-culture assay, as an example, 1

micro-U of hCG was equivalent to 0.0013 micro-U of TSH
 Thyroid physiology 
 The serum TBG concentration rises twofold during the
first trimester of pregnancy and reaches its zenith at
about 20 weeks,because estrogen both increases TBG
production and sialylation; which results in reduced the
clearance of TBG .

 To maintain adequate free thyroid hormone concentrations

during this period, thyroxine (T4) and triiodothyronine (T3)
production by the thyroid gland must increase. Total T4 and
T3 concentrations rise during the first half of pregnancy,
plateauing at approximately 20 weeks of gestation, at which
time a new steady state is reached and the overall production
rate of thyroid hormones returns to prepregnancy rates.  
 Thyroid physiology 
 An increase in (TBG) resulting, TSH secretion is
modestly reduced in the first trimester in response
to the thyrotropic effects of rising human chorionic
gonadotropin concentrations, and may be modestly
increased at term.

 TBG excess leads to an increase in both serum total

thyroxine (T4) and triiodothyronine (T3)
concentrations, by decreasing the circulating pool
of extra-thyroidal free iodide  T4 and T3 , but not
the physiologically important serum free T4 and T3
concentrations
 Serum hCG concentrations ↑soon after fertilization and peak
at 10 to 12 weeks.

 During this peak, total serum T4 and T3 concentrations↑.

 Serum free T4 and T3 concentrations ↑slightly, usually within

the normal range, and

 serum TSH concentrations are appropriately ↓.

 However, in 10 to 20 percent of normal women, serum TSH

concentrations are transiently low or undetectable especially
in women with extremely high hCG concentrations.
 In a report of 63 women with extremely high hCG
concentrations ( >200,000 IU/L, 
 TSH was <0.2 micro U/mL in 67% of samples and
 free T4 was above 1.8 ng/dL in 32 % of samples.
 All women whose hCG was greater than 400,000 IU/L had a
suppressed TSH concentration
 This transient, usually subclinical, hyperthyroidism should be
considered a normal physiologic finding.
 It is not known if this action of hCG benefits the mother or
fetus. Later in pregnancy, as hCG secretion declines, serum
free T4 and T3 concentrations decline and serum TSH
concentrations rise slightly to or within the normal range.
 Thyroid physiology 
 TBG Increases , Beginning early in 1st trimester and, reaches its zenith at
about 20 weeks, and stabilizes at approximately double baseline values
for the remainder of pregnancy.

 Total serum thyroxine (T4) increases sharply beginning between 6 and 9

weeks and reaches a plateau at 18 weeks.

 Free serum T4 levels rise slightly and peak along with hCG levels, and
then they return to normal.

 The rise in total triiodothyronine (T3) is more pronounced up to 18

weeks, and thereafter, it plateaus.

 Thyroid-releasing hormone (TRH) levels are not increased during

normal pregnancy, but this neurotransmitter does cross the placenta and
may serve to stimulate the fetal pituitary to secrete thyrotropin
 Thyroid physiology 
 fall in serum free T3 and T4 concentration, and
 a small rise in serum TSH concentrations
 Free T4 and Free T3 remain normal

 The size of the thyroid gland remains normal during

pregnancy; thus, the presence of a goiter should
always be investigated.
 There is slight thyromegaly 


Small amounts of TRH /T4 cross the placenta  so fetal

thyroid active by 12 weeks gestation 
 thyroid Anatomical changes
 Anatomically, the thyroid gland undergoes moderate
enlargement during pregnancy caused by glandular
hyperplasia and increased vascularity.
 mean thyroid volume increased from 12 mL in the first
trimester to 15 mL at delivery (Glinoer and colleagues
(1990)
 Such enlargement is not pathological, but normal
pregnancy does not typically cause significant
thyromegaly. Thus, any goiter should be investigated.
Trimester-specific reference ranges
of TSH
Because of the changes in thyroid physiology during
pregnancy, the Guidelines of the American Thyroid
Association (ATA) for the Diagnosis and Management of
Thyroid Disease During Pregnancy and Postpartum
recommend using trimester-specific reference ranges for
TSH and method and trimester-specific reference ranges
for serum free T4.
 First trimester 0.1 to 2.5
 Second trimester 0.2 to 3.0
 Third trimester 0.3 to 3.0
 Iodine requirements 
  Iodine requirements are higher in pregnant than in
nonpregnant women due to the increase in maternal
T4 production required to maintain maternal
euthyroidism and increased renal iodine clearance.
 Severe maternal iodine deficiency during pregnancy
results in a reduction in maternal thyroxine
production, inadequate placental transfer of
maternal thyroxine, and impairment of fetal
neurologic development. However, markedly
excessive iodine intake may also be harmful as it can
lead to fetal hypothyroidism and goiter.
 Iodine requirements 
 (WHO) recommends 250 mcg of iodine daily
during pregnancy and lactation.
 ADRENAL GLAND 
 The adrenal glands do not undergo morphologic changes
during pregnancy.

 Adrenal steroidogenesis leads to the production of three

types of steroids:
1. Mineralocorticoids: are synthesized in the zona glomerulosa
2. Glucocorticoids: are produced in the zona fasciculata; and
3. Sex steroids: come from the zona reticularis
 Aldosterone
 The renin-angiotensin system is the primary determinant of adrenal aldosterone
secretion, although ACTH and hyperkalemia also play a role

 As early as 15 weeks, the amounts of aldosterone production in maternal adrenal

glands considerably increased.

 By the third trimester, about 1 mg/day is secreted.

 If sodium intake is restricted, aldosterone secretion is elevated even further

(Watanabe and co-workers, 1963).

 Simultaneously, levels of renin and angiotensin II substrate normally are increased,

especially during the latter half of pregnancy.

 This scenario gives rise to increased plasma levels of angiotensin II, which by acting
on the zona glomerulosa of the maternal adrenal glands, accounts for the markedly
elevated aldosterone secretion.

 the increased aldosterone secretion during normal pregnancy affords protection

against the natriuretic effect of progesterone and atrial natriuretic peptide.
 Aldosterone
 The renin-angiotensin-aldosterone system is stimulated during pregnancy
because of the associated :
1. reductions in vascular resistance
2. reductions blood pressure and
3. the progressive decline in vascular responsiveness to angiotensin II .

 A striking increase in aldosterone levels is observed by the eighth

week of pregnancy and continues to rise to 80 to 100 ng/dl in the
third trimester,

 4—6 fold above the upper limits observed in euvolemic nonpregnant

adults.

 The blood pressure is usually 10 mmHg below baseline in the second

trimester, declining to a mean of 105/60 mmHg.
 the concentration changes of aldosterone are parallel
the serum concentrations of progesterone (produced by the
placenta), which competes with aldosterone for binding to
the mineralcorticoid receptor and therefore has a natriuretic
effect, are increased throughout pregnancy, reaching a level
of 200 ng/dl by term.
 Some investigators have postulated that high plasma
levels of aldosterone during pregnancy reflect a
compensatory response to salt-losing factors, such as
progesterone, and the increased filtration of
extracellular fluid by the kidney.
 Cortisol
 The serum concentration of circulating cortisol is
increased, but the free portion is decreased because
much of it is bound by transcortin, the cortisol-
binding globulin.
 The rate of adrenal cortisol secretion is not increased,
and probably it is decreased compared with that of the
nonpregnant state.
 The metabolic clearance rate of cortisol, however, is
lower during pregnancy because its half-life is nearly
doubled over that for nonpregnant women (Migeon
and associates, 1957). Administration of estrogen,
including most oral contraceptives, causes changes in
serum cortisol levels and transcortin similar to those
of pregnancy.
Musculoskeletal and dermatologic

 Maternal physiology undergoes many changes

during pregnancy. These changes, which are
largely secondary to the effects of progesterone
and oestrogen, begin as early as 4 weeks
gestation and are progressive. In the first 12
weeks of pregnancy progesterone and oestrogen
are produced predominately by the ovary and
thereafter by the placenta. These changes both
enable the fetus and placenta to grow and
prepare the mother and baby for childbirth.
 Skeletal changes

 Increased lumbar lordosis

Lordosis of pregnancy~ progressive increase in anterior
convexity of the lumbar spine

 Preserves center of gravity

 Relaxation of pelvic joints and ligaments due to

progesterone and relaxin
 Ligaments of the symphysis and sacroiliac joints
 Skin changes
Pigmentation:
due to increased melanocyte stimulating hormone:
linea nigra: pigmentation of the linea alba, more marked below
the umbilicus
Chloasma gravidarum: Butterfly pigmentation of the face
(mask of pregnancy)

Striae gravidarum
 stretch of the abdominal wall

rupture of the subcutaneous elastic fibers

pink lines in flanks
 become white after labor