PHYSIOLOGY OF PREGNANCY

Outline
Normal changes in:
Cardiovascular
Volume homeostasis
Hematologic
Respiratory
Endocrine
Urinary
Gastrointestinal

Implications for pathological conditions.

Pregnancy as a “stress test for life”
Introduction
Introduction
Pregnancy is a time when the normal female adult will
re-adjust all her systems to maximize nutrition and
oxygen to the developing fetus and help the
maternal system adjust to the extra stress.
Maladjustment usually leads to the pathological
conditions that occur during pregnancy.
CARDIOVASCULAR CHANGES
 Cardiovascular Changes
These changes are geared to meet the increased metabolic
demands.
The changes are:
Earliest change is peripheral vasodilatation.
Results in
decreased systemic vascular resistance→ allows
↑CO 6 L/ min. Max. (22-28)wks.
Reversible cardiac hypertrophy in 50% of the women
heart rate increase (10-20%).
stroke volume increase (10%).
cardiac out put increase (30-50%).
Mean arterial blood pressure decrease (10%).-
Peripheral resistance decrease (35%)
Cardiovascular – Cardiac output (CO)
Maternal cardiac output increases about 30-50%
during pregnancy (mean 33%)
pregnancy maximum of 6 L/min
CO remains maximal until delivery
Earliest rise in CO is due to increase in SV
As pregnancy progresses
 Gradual increase in maternal HR (15-20 bpm rise)
 SV declines to near non-pregnant levels
 increase HR is what maintains the elevated CO
Cardiovascular – Cardiac output
CO is position dependent
Lower when supine
 IVC compression by the uterus reduces venous return to the
heart
At 38-40 weeks, there is a 25-30% fall in CO when
turning from the side to the back
Fall in CO is compensated by a rise in peripheral
vascular resistance
 supine hypotensive syndrome (1-10% patients)
Cardiovascular – Cardiac output
Distribution of CO
First trimester and non-pregnant state
 Uterus receives 2-3%
By term
 Uterus receives 17%
 Breasts 2%
Reduction of the fraction of CO going to the splanchnic
bed and skeletal muscle
CO to the kidneys, skin, brain and coronary arteries does
not change
Cardiovascular – Arterial BP
BP varies with position

Peripheral vascular resistance falls during

pregnancy
 Progesterone’s smooth muscle relaxing effect
 ?heat production by the fetus  vasodilatation

The reduction in PVR may lead to a progressive

fall in systemic arterial bp during the first 24
weeks of pregnancy
Gradual rise after 24 weeks non-pregnant levels
by term
Cardiovascular – Venous system
Venous compliance increases during pregnancy
decrease in flow velocity and stasis
?progesterone effects on smooth muscle
Forearm venous pressure increases by 40-50%
Calf venous pressures are always higher
 due to the enlarging uterus
Cardiovascular - LV function
Left ventricular dimensions and volume increase
during pregnancy
most parameters of LVF are the same as in the non-
pregnant state
 Ejection fraction, rate of internal diameter shortening, percentage
of fractional shortening, and ventricular wall thickness
Bottom line: preservation of myocardial function
Signs and Symptoms of Normal Pregnancy
Symptoms
reduced exercise tolerance
dyspnea

Signs
peripheral edema
distended neck veins
point of maximal impulse displaced to the left
Signs and Symptoms of Normal Pregnancy
Auscultation
increased splitting of the first and second heart sound
S3 gallop
SEM along the left sternal border
Continuous murmurs
normal changes in heart sounds during pregnancy:
 increase loudness of both S1 & S2.
 >95% develop systolic murmur which disappears after
delivery.
 20% have a transient diastolic murmur.
 10% develop continues murmur due to increase mammary
blood flow.
 ectopics
 Relative tachy cardia
 collapsing pulse
Signs and Symptoms of Normal Pregnancy
CXR
straightening of left heart border
heart position more horizontal – may appear as
cardiomegaly on cxr
increased vascular markings in lungs
ECG
left axis deviation
non-specific ST-T wave changes
Cardiovascular - Labor
First stage of labor: 12-31% rise on CO due to an
increase in SV
Second stage of labor: 34% increase in CO
Not only pain-related
UCs result in the transfer of 300-500 cc of blood from
the uterus to the general circulation
 Enhanced venous return to the heart
 Increase in CO by 10-15%
Cardiovascular - Postpartum
Immediate pp period: 10-20% rise in CO
release of obstruction of venous return
extracellular fluid mobilization
Rise in CO associated with reflex bradycardia
SV increases  this may persist for one to two weeks
after delivery
CHANGES IN VOLUME
HOMEOSTASIS
 VOLUME HOMEOSTASIS
 Fluid retention is the most fundamental systemic
changes of normal pregnancy.
 the total blood volume is increased during pregnancy
30%.
 the most marked expansion occurs in extra cellular
volume (ECV) with some increase in intra cellular
water.
VOLUME HOMEOSTASIS
TBW increases from 6.5L to 8.5L
At term water content of fetus, placenta
and AF is 3.5L
BV, PV, RBC, extra-vascular, intracellular
Pregnancy is a condition of chronic volume overload
Water retention exceeds Na retention-decreased
plasma osmolality
VOLUME HOMEOSTASISS

Blood volume increases progressively from 6 to 8

weeks’ gestation
maximum volume at 32 weeks - 45% increase
possibly due to estrogen stimulation of renin-
angiotensin-aldosterone system
The factors contributing including:

 Increase sodium retention.

 Decrease in plasma osmotic pressure.
 Decrease in thirst threshold.
 Resetting of osmostate.
 Decrease in plasma oncotic pressure.
HEMATOLOGIC CHANGES
Hematology – RBC mass

 Red blood cell mass increases by

250-450 cc by term
 Increased production
 Possibly hormonally mediated
 Hematology - Iron
Maternal requirement is 1000mg
normal pregnant woman needs to
absorb about 3.5 mg/day of iron
 the goal of iron supplementation is to
prevent maternal iron deficiency
 iron is actively transported to the fetus
Hematologic changes
IMPLICATIONS
The increase in plasma volume and rbc
mass translates into a 45% increase in
circulating blood volume
may protect from hemodynamic
instability
may serve to dissipate fetal heat
production and provide increase renal
filtration
physiologic anemia of pregnancy
may function to decrease blood viscosity
may improve intervillous perfusion?
Hematology
LEUKOCYTES
Peripheral wbc rises progressively during pregnancy
 1st ∆ – mean 9500/mm3 (3000-15,000)
 2nd and 3rd ∆ – mean 10,500 (6000-16,000)
 Labor – may rise to 20-30,000
Rise is due to increase in pmns (demargination)

PLATELETS
Platelets experience a progressive decline but should
remain within normal range
Likely due to increased destruction
Hematology
COAGULATION FACTORS
Increased levels
Fibrinogen (Factor I)
Factors VII through X
No change in prothrombin (Factor II),
Factors V and XII
Decline in platelet count, Factors XI and
XIII
Bleeding time and clotting time are unchanged
in normal pregnancy
RESPIRATORY CHANGES
Respiratory system
 UPPER RESPIRATORY TRACT
 Hyperemic mucosa of nasopharynx
 Estrogen-mediated
 nasal stuffiness and epistaxis
 Polyposis of nose and sinuses may occur and regress after delivery
 “chronic cold”

 MECHANICAL CHANGES
 Configuration of thoracic cage changes early in pregnancy
 Increase in subcostal angle, transverse diameter and circumference of
chest
 With advancing gestation, the level of diaphragm is pushed up
Respiratory system
LUNG VOLUME AND PULMONARY FUNCTION
Respiratory rate is unchanged
Due to elevation of the diaphragm
 Total lung volume decreases (diaphragm) by 5%
 Residual volume decreases (RV) by 20%
 FRC is reduced 20%
No change in FEV1 or the ratio of FEV1 to forced vital
capacity
 Respiratory system
GAS EXCHANGE
Minute ventilation rises 30-40% by late pregnancy
O2 consumption increases only 15-29%
Results in higher PAO2 (alveolar) and PaO2 (arterial)
Normal PaO2: 104-108 mmHg
Fall in PACO2 and PaCO2 levels
Normal PaCO2 level: 27-32 mmHg
Increases gradient of CO2 facilitating transfer from fetus to
mother
Arterial pH remains unchanged
Increased bicarbonate excretion via kidneys
Respiratory system
DYSPNEA OF PREGNANCY
Common complaint
 60-70% of patients
 late first or early second trimester
Likely due to various factors
 reduced PaCO2 levels
 awareness of increased tidal volume of pregnancy
CHANGES IN ENDOCRINE
SYSTEMS
 Endocrine - Thyroid
 The normal pregnant woman is euthyroid
 Changes in thyroid morphology and lab indices
 Estrogen-induced increase in TBG
 Decreased circulating extrathyroidal iodide
 Thyroid enlargement usually not detected by exam
 Normal thyroidal uptake of iodide
 Serum TSH decreases early in gestation
 rises to pre-pregnancy levels by end of first Δ
 T4 increases early in gestation
 role of hCG stimulating the thyroid
 Rise in TBG leads to rise in total T4 and total T3
 active hormones free T4 and free T3 are unchanged

 Free T4 is the most reliable method of evaluating thyroid

function in pregnancy
Endocrine - Adrenal glands
Expansion of the zona fasciculata
site of glucocorticoid production
Plasma corticosteroid-binding globulin (CBG)
rises
due to enhanced liver synthesis
Free plasma cortisol rises
increased production and delayed clearance
Plasma DOC (deoxycorticosterone) rises
fetoplacental unit
DHEAS (dehydroepiandrosterone) decreases
Testosterone is slightly elevated
Increased SHBG and androstenedione
Endocrine - Pancreas
Hypertrophy and hyperplasia of the B cells
Fasting associated with accelerated starvation
maternal hypoglycemia, hypoinsulinemia and
hyperketonemia
due to diffusion of glucose by the fetoplacental unit
Feeding response
hyperglycemia, hyperinsulinemia, hypertriglyceridemia
and reduced tissue sensitivity to insulin
glucose response greater during pregnancy
peripheral resistance to insulin: diabetogenic effect of
pregnancy.
 hPL and cortisol mediated
 greater insulin resistance as the pregnancy advances
Endocrine - Pancreas
Fetus primarily depends on glucose
Facilitated diffusion
carrier-mediated but not energy dependent
process

Active transport of amino acids to the

fetus

Ketones diffuse freely across the

placenta
Endocrine - Pituitary
The pituitary gland enlarges in
pregnancy

proliferation of chromophobe cells on the

anterior pituitary
stalk remains midline
Hormones produced within uterus
human chorionic gonadotrophin (HCG):
it is secreted by trophoblast and can be detected in serum 10
days after conception (RIA).
there is high level of circulating HCG in early pregnancy (to
provide a suitable environment for implantation and
development).
to support corpus luteum secretion of oestrogen and
progesterone in the first trimester until the placenta becomes
able to produce these hormones.
the peak level normally occur in the 12th week .
constant level of HCG in late pregnancy is useful in:
 controlling placental secretion of Estrogen
progesterone.
 suppressing maternal immune system against fetus.
the human chorionic gonadotrophine normally
disappear from urine 7-10 days after delivery of
placenta.
human placental lactogen
it is secreted by syncytiotrophoblast.
Its levels increase when the levels of HCG start
to drop .
HPL has no effect on fetus.
HPL effect on :

1-the breast:
omammary growth during pregnancy.
oproduction of colostrum.
omilk production lactation.
2-proteins:
oHPL stimulates protein synthesis at cellular level.
3-carbohydrate:
ostimulate insulinesecretion .
oinhibit insulin action.
4-fat:
HPL mobilize fat from body store (lypolysis) lead
to increase maternal blood glucose and maternal
tissue can not utilze the glucose so the glucose will
be available for fetus.
Estrogen
it is produced by corpus luteum in early
pregnancy.
it is produced by placenta in late pregnancy.
fetus (liver and adrenal ) provide certain
enzymes which are not produced by placenta.
role of estrogen:
On connective tissue: estrogen leads to
polymerization of mucopoly saccarides of the
ground substance leads to loose connective
tissue mainly in the cervix.
On the protein: estrogen stimulate directly RNA
synthesis lead to protein synthesis.
progesterone
it is production same as estrogen.
it has effect on smooth muscle leads to decrease
muscle excitability leads to muscle relaxation mainly
in uterus.
CHANGES IN RENAL SYSTEM
Renal system
ANATOMY
Kidney enlargement
 increased renal vascular and interstitial volume, R>L
Ureteral and renal pelvis dilatation by 8 weeks
 Right > left
 mechanicalcompression by uterus and ovarian venous plexus
 smooth muscle relaxation by progesterone

Implications
 Increased incidence of pyelonephritis
 difficulty in interpreting radiographs
 interference with studies
Renal system
RENAL HEMODYNAMICS
Effective renal plasma flow (ERPF) and GFR
increase
 Filtration fraction falls
 Returns to normal by late third Δ
Endogenous creatinine clearance increases
 Begins by 5 weeks
Renal system
METABOLITES
increased GFR decline in serum urea and creatinine
BUN – 8-9 mg/dl by end 1st Δ
Decline in serum creatinine
 0.7 mg/dl by end 1st Δ
 0.5-0.6 mg/dl by term
Early decline in serum uric acid levels
 nadir at 24 weeks
 same as nonpregnant level at end of pregnancy due to increased
reabsorption of urate
Renal system
SALT AND WATER METABOLISM
Plasma osmolality begins to decline by 2 weeks after
conception
 reduction in serum sodium and other anions
Sodium loss during pregnancy
 50% rise in GFR
 Progesterone: natriuresis
Renal tubular reabsorption of Na+ increases
(aldosterone, estrogen and deoxycorticosterone)
Sodium homeostasis
Renal system
NUTRIENT EXCRETION
Increase in glucose excretion
 1-10 g glucose excretion per day
 Due to 50% increase in GFR
 implications
 inability to use urine glucose
 susceptibility of pregnant women to UTI
Increase in amino acid excretion during gestation
 no increased protein loss (100-300 mg/24 hr)
Increased urinary loss of folate and vitamin B12
GASTROINTESTINAL CHANGES
Gastrointestinal - Appetite
Increase early 1st Δ

Increase intake 200 kcal by end 1st Δ

 RDA: 300 kcal/day during pregnancy

Sense of taste may be blunted

Pica
check for poor weight gain and refractory anemia
Gastrointestinal - Mouth
 Unchanged pH or production of saliva
 Saliva production is unaltered
 Ptyalism – usually in women with Hyperemesis Gravidarum (HEG)
 due to inability to swallow
 Can lose up to 1-2 L of saliva per day
 Decreasing starchy foods might help

 Gums – edematous and soft

 May bleed after brushing

 Epulis gravidarum
 regress 1-2 mos after delivery
 excise if persistent or excessive bleeding
Gastrointestinal - Stomach
Decreased tone and motility
progesterone
possibly due to decreased levels of motility
Conflicting info about delayed gastric emptying
Reduced tone of the gastroesophageal junction
sphincter
Increased intraabdominal pressure leads to acid reflux
Lower incidence of PUD
may be due to decreased gastric acid secretion delayed
emptying, increase in gastric mucus, and protection of
mucosa by prostaglandins
Gastrointestinal - Small bowel
Reduced motility of small
bowel
increased transit time in the third
trimester and postpartum

Enhanced iron absorption

as a response to increased iron
needs
Gastrointestinal - Colon
Constipation
Mechanical obstruction by the uterus
Reduced motility
Increased water absorption

Portal venous pressure is increased

Dilation of gastroesophageal vessels
 issue in those with preexisting esophageal varices
Dilation of hemorrhoidal veins
 hemorrhoids
Gastrointestinal - Gallbladder
Fasting and residual volumes double in 2nd and 3rd Δ
Slower rate of emptying

Biliary cholesterol saturation increases and

chenodeoxycholic acid decreases
increased risk gallstone formation
Gastrointestinal - Liver
 Liver does not enlarge
 Hepatic blood flow remains unchanged
 CO to the liver decreases by ~35%
 Spider angiomata and palmar erythema
 elevated estrogen levels
 Lab data
 Drop in serum albumin
 Rise in serum alkaline phosphatase
 placental production and some hepatic production
 Rise in serum cholesterol, fibrinogen, ceruloplasmin, binding
proteins for corticosteroids, sex steroids, thyroid hormones, and
vitamin D
 No change in serum bilirubin, AST, ALT, protime and 5’
nucleotidase
 Rise in GGT is controversial
Gastrointestinal system
NAUSEA AND VOMITING
Morning sickness complicates 70% of pregnancies
Onset 4-8 weeks up to 14-16 weeks
Cause?
 Relaxation of smooth muscle of stomach, elevated levels of
steroids and hCG
 Rx – supportive: reassurance, support, and avoiding triggers…
Hyperemesis Gravidarum
 weight loss, ketonemia, electrolyte imbalance and dehydration
 possible renal or hepatic damage
 IVF, antiemetics
 NPO
 continue IV
SKIN CHANGES
Skin
Spider angiomata (face, upper chest, and arm) and
palmar erythema
elevated estrogen levels
both regress after delivery

Striae gravidarum

Increased eccrine sweating and sebum excretion

Skin
Hyperpigmentation
Melasma: “mask of pregnancy”
elevated e2 and p4
Nevi may darken, enlarge or show increased activity
rapidly changing nevi should be excised
Hairs in telogen phase decrease in late pregnancy
increases after delivery
hair loss 2-4 mos pp
re-growth in 6-12 mos
Masculinization of the skin rarely occurs
evaluate for possible luteomas of pregnancy (which
regress after delivery)
Breasts
Early change
tenderness, tingling and heaviness
vascular engorgement leads to enlargement
 Ductal growth due to e2
 Alveolar hypertrophy due to p4
Enlargement and pigmentation of areolae
Colostrum may be expressed later in pregnancy
Milk production
E2, p4, prolactin, hPL, cortisol and insulin
Lactation likely due to drop in estrogen and progesterone
after delivery
Skeleton
Total serum calcium declines throughout
pregnancy until 34-36 weeks
due to the fall in serum albumin
Serum ionized calcium is constant and unchanged
“Physiologic hyperparathyroidism”
 increased gut absorption
 decreased renal losses
 no bone loss seen in bone density studies
preservation due to calcitonin?
Rate of bone turnover and remodeling increases
throughout pregnancy
twice as great at term
Eye

Increased thickness of cornea due

to fluid retention (contact lens
intolerance)

Decreased intraocular pressure