CHAPTER 4- MATERNAL PHYSIOLOGY

REPRODUCTIVE TRACT Uterine contractions:

UTERUS - Lower uterine blood flow proportionally to contraction intensity
Nonpregnant Pregnant - Resistance to blood flow in maternal fetal vessels is greater during second
Weight 70g, almost solid Nearly 1100g stage of labor
Capacity w/ cavity of <=10mL Total volume of
contents = 5L but may Uteroplacental Blood Flow Regulation
be 20L (500-1000x Vessels that supply uterine corpus: Spiral arteries that supply placenta
greater capacity) - Widen and elongate - Vasodilate but completely lose
Mechanism: - Preserve contractile function contractility
- Uterine enlargement involves stretching and marked hypertrophy o From endovascular
- Fibrous tissue accumulates trophoblast invasion
- Walls of corpus thicken then gradually thin Mechanism:
o By term only 1-2cm thick - Blood flow increases proportionally to the fourth power of the radius of the
Uterine hypertrophy: vessel
- Action of estrogen and perhaps progesterone - Downstream vascular resistance → accelerates flow velocity and shear
- By 12 weeks’ gestation, related predominantly to pressure exerted stress in upstream vessels → circumferential vessel growth
- Enlargement is most marked in the fundus - Nitric oxide – factors that augment NOS:
- Myometrium surrounding placental site grows more rapidly o Estrogen
o Progesterone
Myocyte Arrangement o Activin
Three strata o PIGF and VEGF
- Outer hoodlike layer – arches over fundus ▪ Attenuated in response to sFlt-1 → pre-eclampsia pathogenesis
- Middle layer – dense network perforated by blood vessels - Vascular refractoriness to pressor effects of infused angiotensin II
o Most - Other factors that augment:
o Myocyte has a double curve – interlacing forms figure eight o Relaxin
- Internal layer – sphincter-like fibers around fallopian tube orifices and o Adipocytokines
internal cervical os ▪ Chemerin – secreted by placenta and increase umbilical eNOS
activity
Uterine Shape and Position ▪ Visfatin – raises VEGF secretion and VEG receptor 2
Uterine Shape Shape expression
First few weeks Piriform or pear shape → ▪ Leptin, resistin, adiponectin – all enhance umbilical vein
endothelial proliferation
globular
- mIR-17 -19 cluster and miR-34 – spiral artery remodeling and invasion
By 12 weeks’ gestation Spherical → ovoid
End of 12 weeks Extends out of the pelvis
CERVIX
Uterine Position
Change Mechanism Purpose
Uterine ascent Rotates to the right
By 1 month, Cervix Increased vascularity Aids in retention of
- Exerts tension on broad
begins to soften and and edema from pregnancy and repair
and round ligaments
gain bluish tone changes in the and reconstitution
Standing Longitudinal axis of uterus collagen network, and postpartum
corresponds to an extension hypertrophy and
of the pelvic inlet axis hyperplasia of cervical
Supine Uterus rests on vertebral glands
column and adjacent great Cervical ripening Lowers collagen and
vessel proteoglycan conc’n
and raises water
UTERINE CONTRACTILITY content
Uterine Contractions Cervical glands - Produces mucus to
Early pregnancy Irregular; mild cramps proliferate and extends obstruct cervical canal;
Second trimester Detected by bimanual exam (eversion) onto Rich in Ig and
5-25 mmHg ectocervical portion cytokines
Near term Braxton-Hicks contractions are Basal cells prominent Estrogen induced Occur together; makes
infrequent in size, shape, staining differentiating them
Last week or two Contract as often as every 10-20 quality from atypical glandular
minutes Arias-Stella reaction: cells difficult
Electrical activity Endocervical gland
- More intense and synchronized by term hyperplasia and
- Develop twice as fast in multiparas hypersecretory
- Account for false-labor appearance
Terms:
UTEROPLACENTAL BLOOD FLOW - Bloody show – when mucus plug is expelled
- Placental perfusion depends on total uterine blood flow - Beading – poor crystallization of cervical mucus spread and dried on a
Midtrimester 450mL/min glass slide
At 36 weeks 500-750mL/min o Due to progesterone
- Increased venous caliber and distensability - Ferning – amniotic fluid leakage causing arborization of ice-like crystals
o Can result in uterine vein varices seen microscopically
o May rupture rarely

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OVARIES Vaginal walls For distention Epithelial thickening,
Change/Mechanism Notes CT loosening, smooth
Ovulation ceases muscle hypertrophy
Single corpus luteum 1st 6-7 weeks of Surgical removal
pregnancy and 4-5 before 7 weeks → Pelvic Organ Prolapse
weeks postovulation spontaneous abortion W/ uncomplicated spontaneous vaginal delivery:
Decidual reaction – From subcoelomic Bleed easily and 1. Vaginal lengthening
usually observed at mesenchyme or resemble freshly torn 2. Posterior vaginal wall and hiatal relaxation
cesarean delivery endometriotic lesions adhesions 3. Increased levator hiatal area
that have been 4. Greater first-trimester vaginal elastase activity
stimulated by All women show greater hiatal distensibility after delivery
progesterone Apical vaginal prolapse:
Enormous caliber of From 0.9-2.6cm at - Prolapse of cervix
ovarian veins term - Cervix may be drawn up w/ uterus as it rises above pelvis
Relaxin - Incarceration may develop at 10-14 weeks’ gestation
- Secreted by: - Expressed in: - Preventive: Uterus replaced early + use of pessary
o Corpus luteum o Brain Attenuation of anterior vaginal wall support:
o Decidua o Heart - Cystocele – Prolapse of bladder
o Placenta o Kidney - Urinary stasis → infection
- Functions: Stress urinary incontinence (SUI)
o Remodels reproductive-tract tissue - Urethral closing pressures do not rise sufficiently
o Initiates augmented renal dynamics - Risk factors in primigravidas:
o Lowers serum osmolality o Maternal age >30
o Increases arterial compliance o Obesity
o Do not contribute to greater peripheral joint laxity or pelvic girdle pain o Smoking
o Constipation
Theca Lutein Cyst o Gestational DM
Hyperreactio luteinalis – exaggerated follicle stimulation Attenuation of posterior vaginal wall
- Moderately to massively enlarged bilateral cystic ovaries - Rectocele
- Linked to markedly elevated serum hCG o May fill with feces → evacuated only digitally
- Found frequently with: o Can block fetal descent unless emptied and pushed out of the way
o gestational trophoblastic disease - Enterocele – hernial sac and contents gently reduced if mass interferes
o Preeclampsia and hyperthyroidism → risk for FGR and preterm birth with delivery
- Also with placentomegaly that accompanies:
o Diabetes BREASTS
o Anti-D alloimmunization Changes
o Multifetal gestation Early Pregnancy Breast tenderness and paresthesias
Symptoms: Second month Breast grow, delicate veins visible
- Abdominal pain – from hemorrhage into cyst Nipples – deeply pigmented, more erectile
- Virilization (30%) from elevated androstenedione and testosterone
o Temporal balding First few months Colostrum can be expressed
o Hirsutism Areolae become broader and more deeply
o Clitoromegaly pigmented
Diagnosis: Bilateral enlarged ovaries containing multiple cysts Glands of Montgomery – scattered through each
Management: Self-limited and resolves after delivery areola
Gigantomastia – pathologically enlarged breasts
FALLOPIAN TUBES Prepregnancy breast size does not correlate w/ ultimate volume of breast milk
Myosalpinx – little hypertrophy
Endosalpinx – flattens SKIN
w/ paratubal or ovarian cyst – may twist ABDOMINAL WALL
Changes Description
VAGINA AND PERINEUM Striae gravidarum Reddish, slightly depressed streaks on abdominal skin,
Change Appearance Mechanism or stretch marks and sometimes over breasts and thighs
Perineum and vulva Chadwick sign: Violet Greater vascularity Glistening, silvery liens in multiparas
color and hyperemia; Diastasis recti Rectus muscles separate, unable to withstand tension
abundant connective Risk factors for striae gravidarum:
tissue softens - Younger maternal age - Prepregnancy weight
Vagina Form thick, white Elevated cervical - Family history - Weight gain during pregnancy
discharge secretions
pH 3.5-6 Increased lactic acid HYPERPIGMENTATION
by Lactobacilus Change Description Mechanism
acidophilus from Linea nigra Pigmented skin line in Elevated melanocyte-
glycogen stores in the linea alba stimulating hormone;
vaginal epihtelium estrogen and
Chloasma or melasma Brownish patches of
Elevated risk of From hormonal, gravidarum (mask of varying size on the progesterone have
vulvovaginal immunologic changes, pregnancy) face and neck melanocyte-stimulating
candidiasis (2nd and 3rd and from greater effects
trimester) glycogen stores
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VASCULAR CHANGES CARBOHYDRATE METABOLISM
Angiomas Normal pregnancy cx by:
- Vascular spiders, nevus, angioma, telangiectasis 1. Mild fasting hypoglycemia
- On the face, neck, upper chest, and arms 2. Postprandial hyperglycemia
- Red skin papules w/ radicles branching out of central lesions ▪ Due to lower insulin insensitivity and augmented hepatic
- May occur w/ Palmar erythema – lack clinical significance gluconeogenesis
- Consequence of hyperestroginemia 3. Hyperinsulinemia
Increased cutaneous blood flow After oral glucose meal:
- Dissipate excess heat generated by augmented metabolism 1. Prolonged hyperglycemia
2. Hyperinsulinemia
HAIR CHANGES 3. Greater suppression of glucagon
Anagen Catagen Telogen - Ensures sustained post-prandial supply of glucose to the fetus
Period of hair growth Involution Resting period - Insulin sensitivity is 30-70% lower in pregnancy
Lengthens during Increases during Overnight, undergoes accelerated starvation → severe ketoacidosis
pregnancy postpartum - Fasting state:
Telogen effluvium – excessive hair loss in the puerperium o decreased plasma glucose and some amino acids
o higher FFA, TAG, and cholesterol concentrations
METABOLIC CHANGES
Period ↑/↓ Magnitude FAT METABOLISM
Metabolic rate 3rd timester ↑ By 20% Parameters Mechanism
+ 10% w/ twin gestation *Maternal ↑ lipids Increased insulin
Total pregnancy 1st timester ↑ 85 kcal/d hyperlipidemia ↑ lipoproteins resistance and estrogen
energy demand 2nd trimester ↑ 285 kcal/day ↑ apolipoproteins stimulation
(77,000 kcal) 3rd trimester ↑ 475 kcal/day Maternal fat First 2 trimesters: ↑ Lipid synthesis and food
Women accrue fat mass despite increased total energy expenditure w/o accumulation intake
significant change in energy intake **3rd trimester: ↓/ceases Enhanced lipolytic activity,
and decreased lipoprotein
WEIGHT GAIN lipase activity
- Average: 12.5kg or 27.5lb *Most consistent striking change during late pregnancy (↑ in third trimester)
- Most is attributable to: **Favors maternal use of lipid and spares glucose and amino acid for the fetus
o Uterus and its contents Breastfeeding:
o Breasts - drops maternal TAG
o Expanded blood and ECF volumes - increase HDL-C
- Smaller fractions:
o Maternal reserve: Accumulation of water, fat, and protein Leptin
- Secreted by adipose tissue
WATER METABOLISM - Key role in body fat and energy expenditure
- Greater water retention is normal - Important for:
- Drop in plasma osmolality of 10 msOms/kg o Implantation
o Induced by reset of osmotic thresholds for thirst and ADH release o Cell proliferation
At term water content: o Angiogenesis
- 3.5 L – water content of fetus, placenta, and amniotic fluid - Deficiency: Anovulation and infertility
- 3.0 L – from expanded maternal blood volume, uterus, and breast growth - Mutation: Extreme obesity
- 6.5 L – minimum amount of extra water In pregnant women:
o Corresponds to 14.3 lb - Peak during 2nd trimester
Pitting edema - Plateau until term – 2-4x higher than in non-pregnant
- Ankles and legs - “Leptin resistance” – promotes energy storage
- From greater venous pressure below the level of the uterus from partial - Disadvantageous in maternal obesity
vena cava occlusion o Dysregulate inflammatory cascade and lead to placental dysfunction
- Decline in interstitial colloid osmotic pressure also favors edema in obese women
Associated w/ neonatal birthweight: - Increased leptin associated w/: preeclampsia and gestational diabetes
- Body water and fat mass Fetal leptin
- Initial maternal weight and weight gained - Development of pancreas, kidney, heart, and brain
- Fetal levels correlate w/ BMI and birthweight
PROTEIN METABOLISM Other Adipocytokines
Magnitude Produced in: Function Clinical Sig
At term, weight of grown fetus 4 kg and 500g of protein Adiponectin Maternal fat Inversely Reduced w/
and placenta correlate w/ gestational
Uterus as contractile protein, the 500g adiposity; potent diabetes
breasts, and to maternal Hb insulin sensitizer
Amino acid concentration Ghrelin Stomach – in Role in fetal
- Higher in fetal compartment from facilitated transport response to growth and cell
- Tyrosine – essential in preterm neonate hunger; proliferation
Estimated average requirements: Placenta
Early pregnancy 1.22 g/kg/d Visfatin Adipose tissue Growth factor ↑ visfatin and
Late pregnancy 1.52 g/kg/d for B cells leptin → impair
Current recommendations 0.88 g/kg/d Uterine
contractions
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ELECTROLYTE AND MINERAL METABOLISM
Electrolyte Changes Mechanism Iron Requirements
Sodium 1000 mEq retained, ↑ GFR, Threshold for ADH 1000 mg required for normal pregnancy:
↓ serum conc’n release is lowered → - 300 mg – fetus and placenta
promotes water - 200 mg – lost through various normal excretion routes
retention - 500 mg – for 450 mL increase in erythrocyte volume
Potassium 300 mEq retained, ↑ GFR, Expanded plasma o 1 mL of erythrocyte = 1.1 mg of iron
↓ serum conc’n volume - 500-600 mL – blood lost in normal vaginal delivery
Calcium ↓ in circulating protein-bound Follows lowered Distribution
nonionized calcium; ionized albumin concentrations - Most iron is used during the latter half of pregnancy: 6-7 mg/d
is unchanged o Not available from iron stores or diet
Magnesium ↓ - total and ionized o W/o supplemental iron – optimal rise of RBC vol will not develop
Phosphate Within non-pregnant range - Fetal RBC production is not impaired because placenta transfers iron even
Iodine ↑ requirements; ↑ iodide ↑ Maternal thyroxine – if mother is IDA
GFR by 30-50% maintain euthyroidism Non-anemic pregnant women:
and transfer TH to fetus; - Serum iron and ferritin decline after midpregnancy
↑ Fetal TH prod’n in 2nd - Hepcidin levels drop early
half of pregnancy; o Aid iron transfer into maternal circulation
Primary route of o Augment iron transport into the fetus
excretion is through
kidney IMMUNOLOGICAL FACTORS
Fetal skeleton - Microbes – commensal and play a tolerizing and protective role
- 30g of calcium by term – 80% deposited during 3rd trimester - Trophoblast express “nonclassic” MHC known as HLA class Ib – inhibits
o Mediated by 1,25-dihydroxyvitamin D3 – from 2x rise in PTH or PTH- NK cell activity and promotes immune quiescence:
related peptide levels by placenta o HLA-E
- Dietary intake of sufficient calcium is necessary especially in pregnant o HLA-F
adolescents o HLA-G
Wolff-Chaikoff effect – excessive iodine leading to congenital hypothyroidism - Th1- mediated immunity shifts to Th2-mediated immunity
due to autoregulation o Supression of Th1 and T- o Remission of:
- Curb thyroxine production in response to iodide overconsumption cytotoxic cells lower: ▪ RA
▪ IL-2 ▪ MS
HEMATOLOGICAL CHANGES ▪ Interferon-a ▪ Hashimoto thyroiditis
▪ TNF
BLOOD VOLUME
o Upregulation of Th-2 w/c o Th-2 upregulation →
After 32-34 weeks’ gestation: 40-45% above nonpregnant blood volume
increase: promote humoral
- Fetus is not essential
▪ IL-4 immunity
Function:
▪ IL-10 o Systemic lupus may flare
1. Meets metabolic demands of hypertrophied uterus and vascular
▪ IL-13
system
- Cervical mucus – peak levels of IgA and IgG
2. Provides abundant nutrients and elements for rapidly growing
o Creates barrier to ascending infection
placenta and fetus
- IgG is transferred to developing fetus in 3rd trimester
3. Protects mother against impaired venous return
- Ig secreted into breast milk
4. Safeguards mother against parturition-associated blood loss
- Th 17 cells and Treg cells – serve mucosal and barrier immunity
12 weeks Expands by 15% o Th 17 – proinflammatory and express IL-17 and RORs
Midtrimester Period of most rapid growth o Treg express FOXP3 and confer tolerizing activity
3rd trimester Rises at a slower rate - Shift toward T reg CD4
Last several wks Plateau o Starts at 1st trimester
Average increase in erythrocyte volume: 450mL o Peaks in 2nd trimester
- Elevated maternal erythropoietin o Falls toward delivery
- Failure of these CD4 subpopulation alterations → preeclampsia
Hemoglobin Concentration and Hematocrit
- Both decline slightly LEUKOCYTES AND LYMPHOCYTES
- At term: 12.5 g/dL Leukocytosis – reappearance of leukocytes previously shunted out of active
o 5% of women - <11.0 g/dL – abnormal and due to IDA circulation
- 15,000/uL – Upper values
IRON METABOLISM - 25,000/uL – levels during labor and early puerperium
Normal adult women o Also same response in strenuous exercise
Total iron content 2.0 to 2.5 g – most in Hb or Distribution:
myoglobin - Absolute T lymphocytes increase
Iron stores 300 mg - B lymphocyte numbers unchanged
Hepcidin - Ratio of CD4 and CD8 – unchanged
- Homeostatic regulator of iron metabolism
- Rise w/ inflammation but drop w/ iron deficiency and several hormones: Inflammatory Markers
o Testosterone Increase:
o Estrogen - Leukocyte ALP levels – evaluates myeloproliferative disorders
o Vitamin D - CRP – gestational age does not affect levels
o Prolactin - ESR – d/t increased globulins and fibrinogen
- Lower levels = greater absorption - C3 and C4 – 2nd and 3rd trimester

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- Procalcitonin – increase at end of 3rd trimester and through 1st few HEART
postpartum days - Displaced to the left and upward
o Rise in bacterial infections but remain low in viral infections - Rotated on its long axis
- Apex is moved laterally → larger cardiac silhouette
Coagulation and Fibrinolysis - Some degree of benign pericardial effusion
Increase concentrations of ALL CLOTTING FACTORS EXCEPT Factors XI and ECG Changes:
XIII - Slight left-axis deviation – most common
- FXIII (fibrin stabilizing factor) – drop as pregnancy advances - Q waves in leads II, III, and avF
Plasma fibrinogen - Flat or inverted T-waves in leads III, V1-V3
Non-pregnant Pregnancy Normal cardiac sounds;
200-400 mg/dL (Ave: 300 mg/dL) ↑ 50% - 300-600 mg/dL (Ave: 450 1. Exaggerated splitting of 1st heart sound
mg/dL) 2. No definite changes In second sound
Fibrinolytic activity is reduced 3. Loud, easily heard third sound
- Favor fibrin formation → countered by ↑ plasminogen - 90% - systolic murmur intensified during inspiration or expiration
- Net: Procoagulant state - 20% - soft diastolic murmurs
o Ensure hemostatic control - 10% - continuous murmurs
Effect of expanding plasma volume:
Regulatory Proteins - Enlarged cardiac end-systolic and end-diastolic dimensions
Thrombophilias – deficiencies of protein C and S and antithrombin - Septal thickness or ejection fraction does not change
- Account for many thromboembolic episodes during pregnancy - Ventricular remodeling:
Activated protein C + cofactor protein S and favtor V – anticoagulant o Left ventricular mass expansion (30-35%) near term
- Neutralizes Va and factor VIIIa ▪ Increased beginning 26-30 weeks’ gestation
During pregnancy: ▪ Remodeling is concentric and proportional
- Resistance to activated protein C grows ▪ Resolved w/in 3 months of delivery
- Drop in free protein S levels Ventricular function
- Greater factor VIII - Normal as estimated by Braunwald ventricular function graph
Period Magnitude - Efficiency of cardiac work (CO x MAP) – rise by 25%
Protein C B/n 1st and 3rd tri From 2.4 to 1.9 U/mL - Increased O2 consumption d/t increased coronary blood flow
Free protein S From 0.4 to 0.16 U/mL
Antithrombin levels B/n midpregnancy and Decline by 13% CARDIAC OUTPUT
term Position Cardiac Output:
Until 12 hours after Fall 30% from baseline Lateral recumbent position Increases in early pregnancy and remains
delivery elevated during remainder
72h after delivery Return to baseline Supine Reduced d/t diminished venous return and
reduced cardiac filling
Platelets From back onto left side At 26-30w: Rise by 20%
- 250,000/uL → 213,000/uL At 32-34w: Rise by 10%
- Thrombocytopenia – below 2.5th percentile (116,000/uL) Standing Falls as in nonpregnant woman
o Partially due to hemodilution Fetal O2 saturation – 10% higher if woman is in lateral recumbent position
o Platelet consumption is augmented Multifetal pregnancies
- Markers of platelet activation rise w/ gestational age but drop postpartum - CO – augmented further by another 20%
- 1st trimester CO >20% than postpartum values
SPLEEN - CO values: increased additional 15% vs 1 st trimester
Spleen enlarges by up to 50% compared w/ first trimester o 6.31 L/min – 2nd trimester
- Size was 68% greater than non-pregnant controls o 6.29 L/min – 3rd trimester
Cause: - LA and LV end-diastolic diameters are longer
- Increased blood volume
- Hemodynamic changes HEMODYNAMIC FUNCTION IN LATE PREGNANCY
Associated w/ expected increases in: Associated w/ decreases in:
CARDIOVASCULAR SYSTEM - Heart rate - Systemic vascular and
5th week Cardiac output is increased D/t reduced systemic - Stroke volume pulmonary vascular
vascular resistance and - Cardiac output resistance
increased heart rate - Colloid osmotic pressure
6-7th week Brachial systolic BP, diastolic Normal pregnancy is not a continuous “high output” state
BP, and central systolic BP
CIRCUALTION AND BLOOD PRESSURE
lower
Blood pressure value
8th week Apparent changes in cardiac
function Brachial artery pressure Sitting < lateral recumbent position
B/n 10 and Preload rises → larger LA Plasma volume expansion Systolic blood pressure Lateral positions < flexed or supine positions
20 weeks volumes and ejection fractions begins Arterial pressure At 24-26w: Declines and rises thereafter
Resting pulse rate – rises by 10 beats/min during pregnancy Diastolic pressure Decreases more than systolic
Increased heart rate: MAP and arterial stiffness Declines in prepregnant and postpartum time
- Between 12 and 16 weeks and Antecubital venous Remains unchanged
- Between 32 and 36 weeks’ gestation pressure
Ventricular performance is influenced by: Femoral venous pressure Supine: 8 mmHg → 24 mmHg at term
- Decrease in systemic vascular resistance Venous blood flow is retarded except in lateral recumbent position
- Changes in pulsatile arterial flow o Predisposes to: dependent edema, development of varicose veins
and hemorrhoids, and DVT
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Supine Hypotension PULMONARY FUNCTION
- 10% - supine compression of great vessels → supine hypotensive Inc/Dec Magnitude
syndrome Functional residual capacity Decrease 20-30% or
- When supine, uterine arterial pressure is lower than in brachial artery (FRC) 400-700 mL
Expiratory reserve Decrease 15-20%
RENIN, ANGIOTENSIN II, AND PLASMA VOLUME volume 200-300 mL
All components are increased Residual volume Decrease 20-25%
Component Produced by Function 200-400 mL
Renin Maternal kidney and 1st tri BP maintenance *Inspiratory capacity (IC) Increase 5-10%
placenta 200-350 mL
Angiotensinogen Maternal and fetal liver Total lung capacity (FRC+IC) Unchanged/ <5%
(augmented by Decrease
estrogen) Respiratory rate Unchanged
Diminished vascular responsiveness to angiotensin II Tidal volume Increase 0.66 to 0.8 L/min
- Those who became hypertensive developed, but then lost, refractoriness Resting minute ventilation Increase 10.7 to 14.1 L/min
- Progesterone related – women lose refractoriness 15-30 minutes after *Inspiratory capacity: maximum volume that can be inhaled
placenta is delivered FRC and Residual volume – decline progressively d/t diaphragm elevation
- Significant in 6th month
CARDIAC NATRIURETIC PEPTIDES Increase in tidal volume and resting minute ventilation is d/t:
BNP and ANP – secreted by cardiomyocytes in response to chamber-wall - Enhanced respiratory drive d/t progesterone
stretching - Low expiratory reserve
- Provokes natriuresis, diuresis and vascular smooth muscle relaxation - Compensated respiratory alkalosis
- Maintained in nonpregnant range - Decreased plasma osmolality → less respiratory depression
BNP ANP Pulmonary Function
- Increased in preeclampsia - Participate in ECF vol Decreased Unaffected Increased
o Caused by cardiac strain expansion *Total pulmonary Lung compliance Expiratory flow rates
- Elevates aldosterone resistance Max breathing Airway conduction
concentrations capacity **Critical closing volume
PROSTAGLANDINS Forced/timed vital
Role in: capacity
- Control of vascular tone *d/t progesterone
- BP **Lung volume at which airways in dependent parts begin to close during
- Sodium balance expiration
PGE 2 PGI2 Greater oxygen requirements and increased critical closing volume
- Natriuretic - Principal prostaglandin of endothelium - Make respiratory disease more serious during pregnancy
- Elevated in late - Regulates BP and platelet function
pregnancy - Maintains vasodilation
Ratio of PGI:Thromboxane
- Important in preeclampsia pathogenesis

ENDOTHELIN
Endothelin-1 – vasoconstrictor
- Vascular sensitivity is not altered during pregnancy
Stimulated by: Stimulate:
- Angiotensin II - Secretion f ANP
- AVP - Aldosterone
- Thrombin - Catecholamines
Increased levels – play a role in preeclampsia
OXYGEN DELIVERY
NITRIC OXIDE Maternal arteriovenous oxygen difference is diminished because:
Important mediator of placental vascular tone and development 1. Amount of O2 delivered by increased tidal volume exceeds O2
Abnormal: Linked to preeclampsia requirements
2. Total Hb mass and total O2 carrying capacity rise
RESPIRATORY TRACT 3. Cardiac output rises
O2 consumption
Diaphragm Rises 4cm - 20% higher in pregnancy
Subcostal angle Widens - 10% higher in multifetal gestation
Transverse diameter of thoracic cage Lengthens by 2cm - 40-60% higher during labor
Thoracic circumference Increases by 6cm
Diaphragmatic excursion is greater in pregnant ACID-BASE EQUILIBRIUM
Great awareness of a desire to breath is common:
- Interpreted as physiological dyspnea
- From greater tidal volume that lowers blood PCO2 → causes dyspnea
- Induced by progesterone (largely) and estrogen (lesser)
o Progesterone: lowers threshold and raises sensitivity of chemoreflex
response to CO2
Compensation:
- Bicarbonate drops: 26 to 22 mmol/L

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pH: - Creatinine clearance – 30% higher than 100-115 mL/min in nonpregnant
Shift to the left Shift to the right: - Failure of pregnant woman to excrete concentrated urine after withholding
- Bohr effect: Increases affinity - 2,3-DPG offsets Bohr effect fluids for 18h does not necessarily signify renal damage
of maternal Hb for O2
Urinalysis
URINARY SYSTEM Glucosuria – may not be abnormal
KIDNEY - Increased GFR + impaired tubular reabsorptive capacity
Parameter Alteration Clinical Relevance - Search for DM is pursued
Kidney size 1cm longer Returns to normal postpartum Hematuria
Dilatation Hydronephrosis on Can be confused w/ - From contamination during collection
sonogram or IVP (more obstructive uropathy; retained - If not = UTI or infection
marked on right) urine leads to collection errors; - Common after difficult labor or delivery
renal infections are more Proteinuria
virulent; may be responsible - Nonpregnant: Excretion rate of >150 mg/d
for “distention syndrome”; - Pregnant: at least 300 mg/d
elective pyelography should be - Albumin excretion is minimal: 5-30 mg/d
deferred for at least 12w - Proteinuria increases w/ gestational age
postpartum
Renal *GFR and renal plasma Serum creatinine decreases, Measuring Urine Protein:
function flow increase ~50% >0.8mg/dL (>72umol/L) Classic dipstick 24-h collection Albumin/crea or
creatinine already borderline; protein/crea ratio
protein, amino acid, and Easy, Routine, Quantitative, More Single collection,
glucose excretion all increase Anytime specific Collection errors are
Maintenance Decreased bicarbonate Serum bicarb: decreased by 4- avoided
of acid-base threshold; progesterone 5 mEq/L; Pco2 decreased 10 Fails to account for Affected by urinary Obtained quickly and
stimulates respiratory mmHg; a Pco2 of 40 mmHg renal concentration or tract dilatation – error collection errors are
center already represents CO2 dilution of urine in retention and timing avoided
retention Threshold to define
Plasma Osmoregulation altered; Serum osmolality decreases abnormal vary
osmolality osmotic thresholds for 10 mOsm/L (serum Na ~5
AVP release and thirst mEq/L) during normal URETERS
decrease; hormonal gestation; increased placental Laterally displaced at the pelvic brim
disposal rates increase metabolism of AVP may cause - Above: Elevated intraureteral tonus → ureteral dilatation is impressive
transient diabetes insipidus o Right sided – 86%
*25% by 2nd week and 50% by 2nd trimester o Progesterone has additional effect
2 principal factors for hyperfiltration: Right ovarian vein
1. Hypervolemia-induced hemodilution lowers protein and oncotic - Lies obliquely over right ureter
pressure - May contribute to right ureteral dilatation
2. Renal plasma flow increased by 80% before the end of 1 st tri
Consequence of elevated GFR: BLADDER
- 60% nulliparas – urinary frequency After 12 weeks’ gestation:
- 80% nulliparas – nocturia - Hyperplasia of bladder muscle and CT → elevate trigone and thicken its
intraureteric margin
- Bladder mucosa – increase in size and tortuosity of blood vessels
Bladder pressure in primigravidas:
- 8 cm H2O – early pregnancy
- 20 cm H2O – term
Urethral lengths
- Absolute – 6.7 mm
- Functional 4.8 mm
- 70-93 cm H2O – maximal intraurethral pressure
Near term:
- Entire base of bladder is pushed ventral and cephalad → difficulties in
diagnosing and treatment procedures
- Pressure from presenting part impairs blood and lymph drainage from
bladder base → edematous area → easily traumatized → susceptible to
infection

Relaxin GASTROINTESTINAL TRACT

- Mediate increased GFR and renal blood flow Stomach and intestines – displaced cephalad
- Boosts renal NO production → renal vasodilation Appendix – displaced upward and somewhat laterally; sometimes right flank
- Increase vascular gelatinase activity → renal vasodilation, glomerular Pyrosis (heartburn)
hyperfiltration, and reduced myogenic reactivity - Most likely caused by reflux of acidic secretions
Maternal posture: - Cause:
- Na excretion in supine – less than half that in lateral recumbent o Altered stomach position
o LES tone decreased
Renal Function Test o Intraesophageal pressures are lower and intragastric pressures
- From 0.7 to 0.5 mg/dL higher in pregnant
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o Esophageal peristalsis has lower wave speed - Promotes mammary alveolar cell RNA synthesis, galactopoiesis, and
Gastric emptying time – unchanged production of:
- During labor, after administering analgesic → prolonged → could result in o Casein
aspiration o Lactalbumin
Hemorrhoids o Lactose
- Caused by constipation and elevated pressure in rectal veins o Lipids

LIVER Oxytocin and Antidiuretic Hormone

- Hepatic and portal venous blood flow increase - ADH levels do not change
Lab test:
Increased Decreased THYROID GLAND
*Total ALP – doubles AST, ALT, GGT, bilirubin TRH
**Leucine aminopeptidase Albumin (from 4.3 to 3.0 g/dL) - Can cross placenta
***Total albumin levels - Does not rise during pregnancy
Serum globulin levels TSH
*Attributable to heat-stable placental ALP isozymes - a-subunits are identical w/ hCG subunits
**Increased w/ liver disease and in pregnancy - B-subunits – differ in amino acid sequence
***D/t increased plasma volume - Levels decline >80% in first trimester
Has oxytocinase and vasopressinase → transient diabetes insipidus hCG
- Intrinsic thyrotropic activity → cause thyroid stimulation
GALLBLADDER Changes during pregnancy:
Contractility is reduced - Boost production of thyroid hormone by 40 to 100%
- Progesterone impairs contraction by inhibiting CK-mediated smooth - Thyroid undergoes moderate enlargement
muscle stimulation - Mean thyroid volume from 12 mL (1st tri) to 15 mL (term)
- Increased prevalence of cholesterol gallstones TBG
- Principal carrier protein of thyroid hormones
ENDOCRINE SYSTEM - Rise in the first trimester
- Reach zenith at 20 weeks
PITUITARY GLAND
- Double baseline values for the remainder
Enlarges by 135%
o From higher hepatic synthesis (due to estrogen) and lower
- Caused by estrogen-stimulated hypertrophy and hyperplasia of lactotrophs
metabolism rates
o Prolactin levels parallel increasing size
Lactotroph Gonadotrophs Corticotroph Thyrotroph Somatotrophs
Thyroid hormones
- Increase total T3 and T4 but not free T4 and free T3
Increase Decline Constant Constant Suppressed
- B/n 6- and 9-weeks’ gestation: Total serum T4 levels rise
Peak pituitary size: 12mm
o 18 weeks: Plateau
- Then involutes rapidly → normal size by 6 months
- Free T4 levels rise only slightly and peak w/ hCG
- If macroadenoma >=10mm → growth during pregnancy is likely
Fetus
- Relies on maternal T4
Growth Hormone
- Fetal thyroid does not begin to concentrate iodine until 10-12 weeks
Secreted by Range
- Secretion of thyroid hormone by fetal pituitary TSH begins at 20 weeks
1st trimester Maternal pituitary 0.5-7.5 ng/mL - At birth: 30% of T4 in umbilical cord is maternal
gland (nonpregnant range)
6 weeks *Placenta Detectable Thyroid Function Test
10 weeks 3.5 ng/mL Normal Suppression of TSH
14-15 weeks Peaks at 14-15 weeks - Potential failure to identify women with hypothyroidism
28 weeks 14 ng/mL Effect of thyroid regulation alterations:
*By 20 weeks, GH is predominantly from placenta - Do not alter maternal thyroid status
Placental GH - Basal metabolic rate increase by 25%
- Acts w/ placental lactogen to regulate fetal growth
- Differs from pituitary GH by 13 amino acid residues Iodine status
- Secreted by syncytiotrophoblast in a nonpulsatile fashion Low or marginal intake – deficiency manifests as low T4 and high TSH
- Influences fetal growth via IGF-1 For fetus – early exposure is essential for nervous system
o Higher levels: preeclampsia
o Correlates positively w/ birthweight PARATHYROID GLANDS
- Pregnancy is a vulnerable period for osteoporosis
Prolactin
Tenfold greater at term – 150 ng/mL Parathyroid Hormone
- 20-26 weeks’ gestation: 10,000 ng/ML Fetal skeleton – requires 30g of calcium during 3rd trimester
o Thereafter, levels decline and reach nadir after 34 weeks - 3% of total calcium held w/in maternal skeleton
Uterine decidua Augmented maternal calcium absorption – provides additional calcium
- Synthesis site of prolactin - Calcium absorbed – 400 mg/d in third trimester
Drop after delivery even in those breastfeeding - Mediated by 1,25-dhydroxyvitamin D
- Pulsatile bursts – response to suckling o Increased d/ PTH or PTH-rP
Function PTH
- Lactation – principal - Declines during first trimester
- Initiate DNA synthesis and mitosis of glandular epithelial cells and - Rises progressively throughout remainder
presecretory alveolar cells of the breast
- Augments number of estrogen and prolactin receptors

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Calcitonin CENTRAL NERVOUS SYSTEM
- Fetal calcitonin – 2x higher than maternal levels MEMORY
- Fall during pregnancy and rise postpartum Throughout pregnancy and early puerperium are problems of:
- Ca and Mg promotes biosynthesis and secretion - Attention
o Gastric hormones, and food ingestion also increase calcitonin - Concentration
- Memory – limited to third trimester
ADRENAL GLANDS o Quickly resolved following delivery
Cortisol - Poorer verbal recall and processing speed
- Rises but bound by transcortin - Worse spatial recognition memory
- Secretion rate is not elevated MRI:
- Metabolic clearance is diminished → half-life nearly doubled Mean blood volume
ACTH Middle cerebral artery Posterior cerebral artery
- Reduced in early pregnancy Non-pregnant 147 mL/min 56 mL/min
- ACTH + free cortisol rise equally and strikingly as pregnancy progresses Late in pregnancy 118 mL/min 44 mL/min
o Result from “resetting” maternal feedback → Tissue refractories to Pregnancy does not affect cerebrovascular autoregulation
cortisol
o May be from antagonistic progesterone on mineralocorticoids – EYES
cortisol is needed to maintain homeostasis 1. Intraocular pressure drops – attributed to greater vitreous flow
o May be preparation for stress 2. Corneal sensitivity decreased – late in gestation
o Might also influence postpartum behavior and parenting roles 3. Slight increase in corneal thickness – due to edema
o May have difficulty w/ previous comfortable lenses
Aldosterone 4. Krukenberg spindles – brownish-red opacities on the posterior surface of
15 weeks: Increased the cornea
3rd trimester: 1 mg/d is released o Hormonal effects
Latter half of *Renin and angiotensin II substrate rise → acts on zona 5. Transient loss of accommodation
pregnancy glomerulosa to elevate aldosterone
*Protection against natriuretic effect of progesterone and ANP SLEEP
If sodium intake is restricted, aldosterone secretion is even further elevated 12 weeks’ gestation through 2 months postpartum:
1. Difficulty w/ falling asleep
Deoxycortisone 2. Frequent awakenings
By term: near 1500 pg/mL (more than 15-fold increase) 3. Fewer hours of night sleep
- Augmented by kidney production from estrogen stimulation 4. Reduced sleep efficiency
Levels in fetal blood is higher than in maternal blood Sleep apnea is more common in pregnancy especially in obese
Greatest disruption is postpartum:
Androgens - Contributes to postpartum blues or frank depression
Androgenic activity rises:
- Androstenedione and testosterone are increased QUESTIONS:
o Converted to estradiol in placenta → increases clearance rate What is your first question before you interpret the ultrasound?
o Greater plasma sex-hormone-binding globulin levels → retard - When was the LMP?
testosterone clearance o To know what day it is on the cycle
Testosterone concentrations in umbilical cord is undetectable What is the ideal time for transvaginal sonography if cyst is seen from 18th day
- From near complete trophoblastic conversion of testosterone to 17B- from LMP?
estradiol - Day 3-5: corpus luteum has already regressed and endometrium is thin
Dehydroepiandrosterone sulfate
- Lower during normal pregnancy from:
o Extensive clearance through maternal hepatic 16a-hydroxylation and
o Placental conversion to estrogen

MUSCULOSKELETAL SYSTEM
Progressive lordosis – characteristic feature
- Compensates for anterior portion of the enlarging uterus
- Shifts center of gravity back over the lower extremities
Increased mobility in joints:
- Sacroiliac
- Sacrococcygeal
- Pubic joints
Most relaxation takes place in the 1st half of pregnancy
- Create lower back discomfort How to collect urine for urinalysis?
- Some symphyseal separation is likely during labor → >1cm may cause - Midstream clean-catch: catch the midstream without stopping flow
significant pain Why is gastric emptying time prolonged?
Upper extremities: - Due to progesterone: smooth muscle relaxant
- Aching, numbness, and weakness Hyperemesis gravidarum and hyperthyroidism is secondary to:
- From marked lordosis and anterior neck flexion and shoulder girdle - hCG
slumping
o Produces traction of ulnar and median nerves
▪ Latter – mistaken for carpal tunnel syndrome
Joint strengthening
- Complete within 3-5 months
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