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PHYSIOLOGIC OBSTETRICS OLFU

MATERNAL PHYSIOLOGY 1st • End of 12 weeks AOG – enlarged uterus extends out of the pelvis,
Dr. DFE19 it contacts the anterior abdominal wall, displaces the intestines
laterally and superiorly and ultimately reaches almost to the liver
• Uterine ascent – rotates to the right, this dextrorotation likely is
Outline:
caused by the rectosigmoid on the left side of the pelvis,
ü Reproductive Tract
ü Breasts • The uterus rises, tension is excreted on the broad and round
ü Skin ligament
ü Metabolic Changes • Standing position – the longitudinal axis of the uterus corresponds
ü Hematologic Changes to an extension of the pelvic inlet axis, when relax the abdominal
wall supports the uterus and maintain its axis
INTRODUCTION • Supine position – the uterus falls back to rest on the vertebral
• Anatomical, physiological and biochemical adaption to pregnancy column and the adjacent great vessels
– still profound
• Changes begin soon after fertilization and continue throughout
gestation
• Response to physiological stimuli provided by the fetus and
placenta
• Virtually, every organ system undergoes alterations, and these can
appreciably modify criteria for disease diagnosis and treatment
• Understanding of pregnancy adaptations is essential to avoid
misinterpretation
• Physiological changes can unmask or worsen preexisting disease

REPRODUCTIVE CHANGES Uterine Contractility


• Early pregnancy – irregular contractions, painless
Uterus • 2nd trimester – Braxton Hicks contractions
• Non-pregnant women § Unpredictably, sporadically, nonrhythmic, 5 and
§ 70g and almost solid, except for the cavity of 10ml or 25mmHg
less • Last several weeks – infrequent but increase in numbers
• During pregnancy • Last week or two – contracts as often as every 10 – 20 mins and
§ Thin-walled muscular organ of sufficient capacity to with some degree of rhythmicity
accommodate the fetus, placenta and amniotic fluid § May cause some discomfort and account for so-called
§ Total volume of contents – 5L (20L) false labor
§ Weights 1,100g
§ Stretching and marked hypertrophy of muscular cells
Uteroplacental Blood Flow
§ Limited production of new myocytes
• The delivery of most substances essential for fetal and placental
§ Accumulation of fibrous tissue, particularly in the
external muscular layer growth, metabolism and waste removal is dependent on adequate
§ Term – myometrium of 1 to 2cm thick perfusion of the placental intervillous space
§ Stimulated by the action of estrogen and progesterone • Placental perfusion os dependent of total uterine blood flow
§ 12 weeks AOG – pressure exerted by the expanding • 500 to 750ml/min
products of conception • Decrease in uterine blood flow that was approximately
• End of pregnancy proportional to the contraction intensity
§ The uterus has achieved a capacity that is 500-1000x • Factor that decreases uteroplacental blood flow
greater than the non-pregnant state § Low arterial pressure
§ The corresponding increase on uterine weight is such § Uterine contraction
that, by term the organ weights nearly 1100g § Supine position
• Condition associated with decrease placental perfusion
Myocyte Arrangement § Hypertension
• Outer hood-like layer § IUGR
§ Arches over the fundus and extends into the various § DM
ligament § Multiple gestation
• Middle layer
§ Composed of 2 dense network of muscle fibers Uteroplacental Blood Flow Regulation
perforated in all directions by blood vessels • Maternal-placental blood flow progressively increase during
• Internal layer gestation principally by means of vasodilation
§ With • 20 weeks – uterine artery diameter doubled
sphincter-like • Estradiol and progesterone, relaxin
fibers around • Normal pregnancy – characterized by vascular refractoriness to the
the fallopian pressor effects of infused angiotensin II and norepinephrine
tube orifices
and internal Cervix
cervical os • Goodell’s Sign – softening and cyanosis, 1 month after conception
• Increase vascularity and edema of the entire cervix, together with
hypertrophy and hyperplasia of the cervical glands
Uterine Shape and Position • Rearrangement of this collagen-rich connective tissue –
• 1st few weeks – maintain original piriform or pear shape maintenance of a pregnancy to term, dilation to aid delivery and
• 12 weeks AOG – the corpus and fundus become globular and repair following parturition
almost spherical, the organ grows rapidly in length than in width • Estrogen and progesterone metabolism
and becomes ovoid • Normal pregnancy-induced changes – extension or eversion of the
proliferating columnar endocervical glands

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PHYSIOLOGIC OBSTETRICS OLFU
• Endocervical mucosal cells produce copious tenacious mucus that Theca-Lutein Cysts
obstruct the cervical canal soon after conception
§ Rich in immunoglobins and cytokines
§ Acts as an immunological barrier to protect the uterine
contents against infection
§ Bloody show
§ Beading or ferning – Arias-Stella reaction

• Hyperreactio luteinalis
§ exaggerated physiological follicle stimulation
§ associated with preeclampsia and hyperthyroidism
§ risk for fetal growth restriction and preterm birth
• Usually bilateral cystic ovarian are moderately to massive enlarged
– linked to elevated serum hCG
• Found in frequently with gestational trophoblastic disease and can
develop with the placentomegaly that can accompany diabetes,
anti-D alloimmunization and multifetal gestation
Ovaries • Usually symptomatic, hemorrhage into the cyst can cause acute
• During pregnancy – ovulation ceases and maturation of new abdominal pain and virilization of the fetus
follicles is suspended • Maternal virilization 30%
• Corpus luteum – function maximally during the first 6 to 7 weeks of § Temporal balding
pregnancy § Hirsutism
• Extrauterine decidual reaction on a beneath the surface of the § Clitomegaly
ovaries § Associated with elevated testosterone and
• Arises from subcoelomic mesenchyme as a result of progesterone androstenedione
stimulation § Bilateral enlargement ovaries with multiple cyst
• Diameter of the ovarian vascular pedicle increased during § Self-limiting
pregnancy from 0.9cm to approximately 2.6cm at term
Fallopian Tube

• During pregnancy – little tube musculature (little hypertrophy) -


myosalpinx
• Epithelium of the tubal mucosa becomes somewhat flattened
(endosalpinx)
• Decidual cells may developed in the stroma of the endosalpinx
• Rarely – increase size of the gravid uterus, especially in the present
of paratubal or ovarian cyst, may result in fallopian tube torsion

Vaginal and Perineum


• during pregnancy – greater vascular and hyperemia develop in the
skin and muscle of the perineum and vulva, and the underlying
abundant connective tissue softens
• Chadwick’s sign
§ augmented vascularity prominent affects the vagina
and cervix and results in the violet color

Relaxin
• Secreted by the corpus luteum, decidua and the placenta
• Play a key role facilitating many maternal physiological adaptations
• Remodeling of reproduction-tract connective tissues to
accommodate parturition • Bartolin’s gland duct cysts – common
• Normal pregnancy – initiation of augmented renal hemodynamics, • vaginal walls undergoes striking changes in preparation for the
decreased serum osmolality, and increased uterine compliance distention that accompanies labor and delivery
• Do not contribute to increase peripheral joint laxity during • elevated volume of cervical secretion during pregnancy forms a
pregnancy somewhat thick, white discharge
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PHYSIOLOGIC OBSTETRICS OLFU
• pH is acidic – 3.5 to 6, due to production of lactic acid by Hyperpigmentation
lactobacillus acidophilus during glycogen energy stores in the • 90% of women
vaginal epithelium • Linea Alba - dark brown-black pigmentation to form the linea nigra

Note: Events of 1st trimester


• Chadwick’s sign – dusky hue of the vestibule and anterior
vaginal wall (local vascular congestion)
• Osiander’s sign – increased pulsation felt at lateral fornixes (8th
week)
• Goodle’s Sign – marked softening of the cervix (6th weeks)
• Piskaceks’s sign – asymmetrical enlargement of the uterus in
case of lateral implantation • Cloasma or Melasma Gravidarum “the mask of pregnancy” –
• Hegar’s sign – softening and compressibility of the lower irregular brownish patches of varying size appear on the face and
uterine segment (6th to 8th weeks) neck
• Braun Von Fernwald’s Sign – irregular and enlargement at the • Pigmentation of the areola and genital skin may also be
site of implantation other than the cornua accentuated
• Ladin’s Sign – softening of the cervicouterine junction (5th to 6th • Melanocyte – stimulating hormone
weeks) a soft spot noted anteriorly in the middle of the uterus • Estrogen and progesterone
near its junction with the cervix
Vascular Changes
BREAST • Angiomas “vascular spiders”
• early pregnancy – women often experience breast tenderness and § face, neck upper chest and arms – these are minute, red
paresthesia’s skin with radicles branching out from a central lesion
• after 2nd month – the breast grown in size and delicate veins are § often designed as nevus, angioma or telangiectasias
visible just beneath the skin • Palmar Erythema
• nipples become considerably larger, more deeply pigmented and § encountered during pregnancy
more erectile § no clinical significance and disappear in most women
• after 1st few months – thick yellowish fluid (colostrum) can often be shortly after pregnancy
expressed from the nipples by gentle massage § consequence of hyperestrogenemia

Hair Changes
• Anagen phase – human hair undergoes a pattern of cyclic activity
• Glands of Montgomery – scattered through each areola are several
that includes periods of hair growth
small elevations, which are hypertrophic sebaceous glands
• Catagen phase – apoptosis-driven involution
• Gigantomastia – gain extensive sizes, skin striae similar to those
• Telogen phase – resting period
observed in the abdomen, which require postpartum surgical
• During pregnancy, anagen phase lengthens and telogen rate
reduction
increases postpartum
• Telogen effluvium – exaggerated in most gravidas, but excessive
SKIN
hair loss in the puerperium
• Skin changes are common and found at least physiological
cutaneous changes in 89% of examine women

Abdominal Wall
• Striae Gravidarum or stretch marks – occurs after midpregnancy,
reddish, slightly depressed streaks commonly develop in the
abdominal skin and sometimes in the skin over the breast and
thighs
• Multiparous women – glistening, silvery lines that represents the
cicatrices of previous striae
§ Abdomen – 70% METABOLIC CHANGES
§ Breast – 33% • In response to the increased demand of the rapidly growing fetus
§ Thighs – 41% and placenta, the pregnant women undergoes metabolic changes
that are numerous and intense
• 3rd trimester – maternal basal metabolic rate is increased by 10 to
20 % compared with that of the nonpregnant state, additional 10%
to the twin gestation
• Additional total pregnant energy demand associated with
nonpregnant
• 77,000 kcal or 85% kcal/day
• Diastasis Recti – creating rectus muscle separate in midline, the • 475 kcal/day during the 1st, 2nd and 3rd trimester
muscles of the abdominal walls do not withstand the tension of
the expanding pregnancy

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PHYSIOLOGIC OBSTETRICS OLFU

Weigh Gain Fat Metabolism


• Most of the normal increase in weight gain during pregnancy is • Increase concentration of lipid, lipoproteins and apolipoproteins in
attributed to the uterus and its contents, the breast and expanded plasma
blood and extravascular fluid volumes • Maternal hyperlipidemia – increased insulin resistance and
• Maternal reserves – smaller fraction results from metabolic estrogen stimulation
alterations that increase accumulation of cellular water, fat and • Increased lipid synthesis and food intake – maternal fat
protein accumulation during the 1st and 2nd trimester
• 3rd trimester – fat storage decline or ceases
§ Reduction of circulation triglyceride uptake in adipose
tissue
o Enhance lipolytic activity
o Decrease lipoprotein lipase activity
• Catabolic state – favors maternal use of lipids as an energy a source
and spares glucose and amino acids for the fetus
• Late pregnancy – maternal hyperlipidemia, most consistent and
striking changes of lipid metabolism
• Increase in triacylglycerol and cholesterol levels
§ VLDL
§ LDL
§ HDL
Water Metabolism
• After delivery – decrease concentrations of lipid, lipoprotein,
• Increased water retention – normal physiological alteration
apolipoproteins
• Term:
§ Lactation speed the changes in levels
§ 3.5 L – water content of the fetus, placenta and amniotic
fluid
Leptin
§ 3.0 L – maternal blood volume and in the size of the
• Nonpregnant – primarily secreted by adipose tissue, a key role on
uterus and breast
body fat and energy expenditure regulation
• Pitting edema of the ankles and legs is seen n most pregnant
• Deficiency – anovulation and infertility
women, especially at the end of the day
• 2nd trimester – levels increase and reaches its peak
§ Partial vena cava occlusion
• 3rd trimester – levels plateau
§ Decrease in interstitial colloid osmotic pressure
• Increase due to increased maternal energy demands
Protein Metabolism • Help to regulate fetal growth
• Products of conception, the uterus and maternal blood – relatively
rich in protein rather than fat or carbohydrate Ghrelin
• Term: • Expressed in the placenta
§ 500g CHON – fetus and placenta weight 4kg • Principally by the stomach in response to hunger
§ 500g CHON – uterus as contractile protein, breast § Energy homeostasis modulation
maternal blood as hemoglobin and plasma proteins § Fetal growth and cell proliferation
• Amino acid concentrations are higher in the fetal than in the • Midpregnancy – increase and peak
maternal compartment • Term – decrease
§ This regulated by the placenta (protein synthesis, • Decreases:
oxidation and transamination of some nonessential § Metabolic syndrome
amino acids) § Gestational DM

Carbohydrate Metabolism Energy and Electrolyte Metabolism


• Normal pregnancy – mild fasting hypoglycemia, postprandial
hyperglycemia, and hyperinsulinemia Sodium and Potassium
• Several unique responses.to glucose ingestion • Normal pregnancy
§ Consistent with a pregnancy-induced state of peripheral § Na – 1000meq
insulin resistance, the purpose of which is likely to § K – 300meq
ensure a sustained postprandial supply of glucose to the • Glomerular filtration of Na and K due to:
fetus § Enhanced tubular resorption
• Insulin resistance – not completely understood § Expanded plasma volume
§ Progesterone and estrogen § Level remains very near the normal range for non-
§ Placental lactogen – growth hormone like action pregnant women

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PHYSIOLOGIC OBSTETRICS OLFU
Calcium Iron Metabolism and Requirements
• Ionized and nonionized calcium – decline during pregnancy due to: • Storage iron:
§ Protein-bound nonionized calcium – follows reduction § Normal adult women – 2.0 to 2.5g
lowered albumin concentration § Most in incorporated in Hgb or myoglobin
§ Serum ionized calcium levels – remain unchanged § Iron stores of normal young women are only
• Fetal skeleton accretes approximately 30g and Ca by term, 80% of approximately 300mg
this deposited during 3rd trimester • Lower iron level in women may be partially due to menstrual blood
• Developing fetus imposes a significant demand on maternal Ca loss, and gave a role particularly hepcidin – a hormone that
homeostasis functions as a homeostatic regulator of systemic iron metabolism
• Hepcidin
Magnesium § Increase
• During pregnancy o with inflammation
§ Pregnancy is actually a state of extracellular magnesium § Decreases
depletion o with iron deficiency and several hormones
(testosterone, estrogen, vit. D and prolactin)
Phosphate o associated with greater absorption of iron
• Within the nonpregnant range via ferroportin in enterocytes
• Renal threshold for inorganic phosphate excretion is elevated in • Maternal iron
pregnancy due to increased calcitonin levels § Vaginal delivery and the 1st postpartum days – half of
the added erythrocytes are lost from most women from
Iodine the placental implantation site, episiotomy or laceration
• Requirement increases during normal pregnancy and lochia
§ Maternal thyroxine (T4) production increases to • Blood loss
maintain maternal euthyroidism and to transfer thyroid § Vaginal delivery – 500 to 600 mL
hormone to the fetus early in gestation before the fetal § CS or vaginal twin delivery – 1000 mL
thyroid is functioning
§ Fetal thyroid hormone production increases during the Iron Requirements
2nd half of pregnancy, this contributes to increased • Iron requirement:
maternal iodine requirements because iodine readily § 1000mg – requirements for normal pregnancy
crosses the placenta § 300mg – fetus and placenta
§ The primary route of iodine excretions through the § 200mg lost (excreted, GIT)
kidney, beginning in early pregnancy, the iodine § 500mg for the total circulating volume
glomerular filtration rate increases by 30-50% • The amount of dietary iron, together with that mobilization from
• Placenta has the ability to store iodine stores will be insufficient to meet the average demands imposed
• Wolf-Chaikoff effect – autoregulation in thyroid gland, to curb by pregnancy
thyroxine production on response to iodine overconsumption

HEMATOLOGIC CHANGES

Blood Volume
• Normal pregnancy – hypervolemia of 40-45%, above the
nonpregnancy blood volume after 32-34 weeks AOG
• Function of pregnancy-induced hypervolemia:
§ Meets the metabolic demands of the enlarged uterus
and its greatly hypertrophied vascular system
§ Provides abundant nutrients and elements to support
the rapidly growing placenta and fetus
§ Safeguards the mother against the adverse effects pf
parturition-associate blood loss
• 1st trimester – maternal blood volume begins to increase
• 2nd trimester – maternal blood volume expands most rapidly Immunological Functions
• 3rd trimester 0 rises at a much slower rate, and plateaus during the • Pregnancy – associated with suppression of various humoral and
last several weeks cell-mediated immunological functions to accommodate the
• Blood volume expansion results from an increase in both plasma “foreign” semi allogeneic fetal graft
and erythrocytes • Pregnancy is both a proinflammatory and anti-inflammatory
condition:
§ Early pregnancy – pro-inflammatory
o Inflammatory environment is required to
secure cellular debris removal and adequate
repair of the uterine epithelium
§ Midpregnancy – anti-inflammatory
o Period of rapid fetal growth and
development, the predominant
immunological feature is induction of an
anti-inflammatory state
§ Parturition
o Influx of immune cells into the myometrium
Hemoglobin Concentration and Hematocrit to promote recrudescence as of
• Hgb and Hct – decrease slightly during pregnancy inflammatory process
• whole blood viscosity decreases • Important anti-inflammatory component of pregnancy
• Hgb at term – 12.5g/dl § Suppression of T-helper 1 (Th1) and T-cytotoxic 1 (Tc1)
§ Iron deficiency – 5% below 11.0g/dl cells – decrease secretion of interleukin-2 (IL-2),
interferon-g and tumor necrosis factor-b (TNF-b)
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PHYSIOLOGIC OBSTETRICS OLFU
• Suppressed Th1 response – requisite for pregnancy continuation Reference
- William Obstetrics 25th Ed
• Upregulation of Th2 cells – increase secretion of (IL-4, IL-6, IL-13) - Dr. DFE’s19 recording and PPT (2019 lecture)
- SY: 2019-2020
• Cervical mucus – high level of IgA and IgG
• Increase – Interleukin-1b found in cervical and vaginal mucus

Leukocytes and Lymphocytes


• 2nd trimester – depressed polymorphonuclear leukocyte
chemotaxis and adherence function
• Relaxin impairs neutrophil activation
• Leucocyte counts:
§ During pregnancy – 15,000/µL
§ Labor and Puerperium – 25,000/µL (average of 14,000
tot 16,000/µL)
• Altered distribution of cell type
§ 3rd trimester - ­ granulocytes and CD8 T lymphocytes,
CD4 lymphocytes and monocytes

Inflammatory Markers
• Many tests performed to diagnosed inflammation cannot be used
reliably during pregnancy
§ Leucocytes alkaline phosphate
§ C-reactive protein
§ Erythrocyte sedimentation rate (ESR)
§ Complement factors C3 and C4
§ procalcitonin

Coagulation and Fibrinolysis


• normal pregnancy – both coagulation and fibrinolysis are
augmented but remain balanced to maintain hemostasis
• enhanced in multiple gestation
• increased concentration of all clotting factors except factors XI and
XIII
• clotting time of whole blood – does not differ significantly
• physiological increase in plasma volume in normal pregnancy –
increased concentration represent a markedly augmented
production of these procoagulations

Regulation of Proteins
• natural inhibitors of coagulation – protein C and S and antithrombin
– Thrombophilias
• activated protein C – along with the cofactors protein S and factor
V, functions as an anticoagulant by neutralizing the procoagulants
factor Va and factor VIIIa
§ between 1st and 3rd trimester – decreases from 2.4 to
1.9 µ/mL
§ free protein S concentrations – diminish from 0.4 to
0.16 µ/mL
• anti-thrombin levels – decreases by 3-% between midpregnancy
and term, and fall 30% from baseline until 12 hours after delivery
§ after 72 hours after delivery – there is return to baseline
• during pregnancy – resistance to activated protein C increases
progressively and its related to a concomitant decrease in free
protein S and increase in factory VIII levels

Platelets
• normal pregnancy
§ slight decreased in PLT – 213,000/µL
§ hemodilutional effects
• thrombocytopenia – 116,000/µL
• midpregnancy – increase production of thromboxane A2, which
induces PLT aggregation

Spleen
• end of normal pregnancy – enlarges by up to 50% compared with
that in the 1st trimester
• cause – unknown
§ increased blood volume and/or the hemodynamic
changes of pregnancy
• sonographically, the echogenic appearance of the spleen remains
homogenous throughout gestation

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