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Progesterone
"Pro-gestation" hormone
- Synthesis:
- -corpus luteum of ovary (rescued by hCG if fertilzation occurs)
- -placenta during pregnancy (syncytiotrophoblast)
- -synthesized from maternal cholesterol (LDL)

- Functions:
- -suppress myometrial activity
- -relax smooth muscle
- -increase sensitivity to CO2
- -immunomodulation
- -increase Na+ and Cl- excretion
- -substrate for fetal adrenal steroids
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Estrogens
- Estrone
- Estradiol
- Estriol
- Estetrol
- Synthesis:
- 1. Androgen precursors
- -Fetal and maternal adrenal DHEA-S (estrone, estradiol)
- -Fetal 16a-OH-DHEA-S (estriol)
- 2. Placental sulfatase, aromatase
- Maternal Effects:
- -increases uterine blood flow
- -increases hepatic production (binding proteins, coagulation factors)
- -stimulates RAAS (increased aldosterone)
- -sensitize uterus to labor
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Human Chorionic Gonadotropin (hCG)
- The "pregnancy horomone"
- -detectable at day 21 of cycle
- -doubling time 31 hours (sign of viability)
- Dimeric protein
- -a unit (TSH, LH, FSH)
- -thyrotropic
- -b unit (LH)
- Function:
- -luteotropin (maintains CL)
- -essential day 1 to week 10
- -fetal testes, adrenal (androgen, corticosteroid production)
- -immunomodulation (suppresses decidual T cells)
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Chorionic Somatomammotropin (hCS)
- aka: Placental Lactogen (hPL)
- -homology to hGH and prolactin
- -detected by day 21 (rapid half life, 1-4g produced per day)
- Function:
- -modify maternal metabolism
- -insulin agonist (GH-like) (increase available glucose, increase insulin, increase lipolysis and FFA)
- -minimal lactogenic or growth activity
- -non-essential
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Cardiovascular Adaptations
- Critically important
- -delivery of oxygen and substrates to fetus
- -removal of fetal waste
- Uterine blood flow augmented 10-fold
- -increased flow and vascular capacitance
- Changes are rapid, substantial and reversible
- -present in the first weeks of pregnancy
- -plateau at 28-32 weeks
- -augmented in labor
- -generally resolve by 6 weeks postpartum
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Blood Volume
- Increased by 40-50%
- -begins by 4th menstrual week
- -wide individual variation
- -peak at 28-34 weeks
Greater increase with multiples
Failed expansion threatens fetal growth

-most of the expansion is due to increased plasma volume - -can lead to anemia
Return to non-pregnant levels by six weeks postpartum
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Plasma Volume
- Accounts for 3/4 of increased TBV
- -40% average increase
- -1.2-1.6L by 28 weeks
- Mediated by:
- 1. Sodium Retention and Volume Expansion
- -RAAS
- -changed "osmostat"
- 2. Vasodilation
- -estrogen - NO system
- -progesterone effect on venous tone
- -vasodilating prostaglandins
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Cardiac Output
- 30-50% Increase
- -from 5 to 7 L/min
- -half happens by 8 weeks
- -plateau at 20 weeks
- -sustained until delivery
 - Mediated by:
- 1. Rapid increase in SV (due to preload, blood volume)
- 2. Progressive rise in heart rate
- 3. Utero-placental shunt (reduced resistance)
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Systemic Vascular Resistance
- Rapid decrease in SVR
- -nadir 14-24 weeks
- -slow increase until term

- Mediated by:
- 1. Progesterone
- -smooth muscle relaxation (angiotensin resistance)
- 2. Estrogens
- -endothelial products (prostacyclin, NO)
- 3. Compliance Changes
- -collagen remodeling
- 4. Utero-Placental shunt
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Blood Pressure
- Decreased BP
- -DBP > SBP
- -nadir 24-32 weeks
- -normalized at term

- Mediated by:
- -vasodilation (NO, Prostacyclin, estradiol)
- -Shunt
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Regional Blood Flow
- Uterus
- -10 fold increase (from 50 to > 500 mL/min)
- -10-20% of CO

- Renal
- -50-80% increase
- -% of CO stable
- -for waste excretion
- Skin
- -heat dissipation
- -mucous congestion
- Pulmonary
- -vascular markings on CSR
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Cardiovascular Exam Findings
Increased silhouette, enlarged atria
- EKG:
- -rotation of QRS axis, R axis deviation
- -ST segment depression
- -Q waves in III-T wave inversion in III
- -normal rate (NOT tachycardic)
PMI elevated to left
Pulse brisk and full
JVP distention, venous hum
- Heart Sounds:
- -early to mid systolic flow murmur
- -loud and widely split S1
- -S3 murmur
- Skin Vessels:
- -spider angiomas
- -varicose veins
- Vascular Permeability
- -dependent edeam
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Clinical Implications of Cardiovascular Changes
- Common Symptoms:
- -fatigue
- -dyspnea
- -orthopnea
- -pre-syncope
- -dizziness
- -palpitations
- -edema
- Cardiovascular Disease in Pregnancy
- 1. Pregnancy Poorly Tolerated
- -pulmonary hypertension
- -Marfans Syndrome
- -Aortic Coarctation
- *high risk for decompensation, often recommend that they not get pregnant
- 2. Moderate Risk
- -Aortic stenosis
- -Mitral stenosis
- -Prosthetic valves
- -Myocardial infarction
- 3. Low Risk
- -VSD-ASD
- -Corrected Tetralogy of Fallot
- -Ductus arteriosus
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Mitral Valve Stenosis in Pregnancy
-about 60% with moderate to severe stenosis become symptomatic by 30 weeks (at the peak of vascular volume increase)
-critical to control heart rate to preserve stroke volume
-risk of thromboembolism with enlarging left atrium, especially with atrial fibrillation
-monitor volume status closely (need preload but careful not to push into pulmonary edema)
-want to control pain (can push into decompensation)
-hospitalize for up to one week after delivery b/c risk is still elevated at this time
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Respiratory Adaptations
- Anatomic Changes:
- -diaphragm higher (by 10 weeks so not just due to gravid uterus)
- -thorax rounder
- -ribs elevated

- Mediators:
- 1. Progesterone
- -stimulates respiration (increased CO2 sensitivity, increased ventilatory drive)
- -bronchodilation
- 2. Prostaglandin PGE1, PGE2
- -bronchodilators
- Overventilation is beneficial for fetus
- -favors O2 delivery to fetus
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Lung Volumes in Pregnancy
 - TLC: small decrease due to elevation of diaphragm
- TV: increases 30-40%
- -long inhalations and exhalations
- -at the expense of ERV
FRC, ERV and RV decrease
*Pregnant women have a lower reserve and are at increased risk for hypoxia
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Clinical Implications of Respiratory Changes
- Gradients facilitate transplacental exchange
- -removal of CO2 and acids
- -delivery of O2
- Symptoms:
- -dsypnea (60-70%)
- -congestion, rhinitis
- -epistaxis
- Diseases and Exposures:
- -pulmonary edema
- -asthma
- -smoking
- -pneumonia and respiratory failure
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Asthma in Pregnancy
- Unpredictable: improve, no change or worse
- Factors influencing improvement:
- -increase circulating free cortisol
- -decrease bronchomotor tone and airway resistance
- -increase serum cAMP levels
- Factors influencing worse disease:
- -exposure to fetal antigens
- -alterations in cell-mediated immunity
- -hyperventilation
Severe asthma before = severe asthma in pregnancy
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Respiratory Treatment Goals in Pregnancy
- -prevent allergen exposure
- -treat sinusitis, bronchitis
- -avoid strenuous exercise/exposure to cold
- -treat reflux to prevent bronchospasm
- -stop smoking
- -low threshold for oral steroids at onset of URI
- -MDI treatment plan
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Acid-Base Status in Pregnancy
Hyperventilation causes alkalosis
Fetus can handle low PO2 due to HbF
Fetal umbilical vein contains oxygenated blood
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Hematologic Adaptations
- Anemia of pregnancy:
- -primary dilutional (third trimester catch up)
- -increased RBC mass (increased Epo)
- -iron deficiency (33% decrease in maternal Fe)
- -fetus can also be affected by iron deficiency (often supplement)

Leukocytosis
Thrombocytopenia
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Hemostatic Adaptations
- Thrombophilic state of pregnancy
- -increased coagulation factors (fibrinogen, VII, VIII, X, vWF)
- -increase contact factors (XII, HMWK, prekallikrein)
- -increase fibrinolytic inhibitors (PAI-1, PAI-2)
- -decrease anticoagulation factors (protein S, protein C)
- Clinical Implications:
- -10 fold risk of VTE
- -but provides improved hemostasis at delivery
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Diagnosis of PE in Pregnancy
- CT scan
- -dose and timing
- -first trimester
Angiogram
Lower extremity U/S
D-dimer
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Anticoagulation in Pregnancy
- Coumadin
- -known teratogen
- -can be prescribed for breast feeding women
- Levonox
- -can be given til 36 weeks, then heparin
Delivery planning
Resume anticoagulation post partum through 6 weeks
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Thyroid Axis Adaptations
- Euthyroid hyperthyroxinemia
- -hCG stimulates the thyroid
- -estrogen increases thyroid binding globulin
- -increase total T3 and T4
- -slight increase in free T3 and T4
- -slight decrease in TSH
- -increase thyroid hormone 40-100%
- Maternal Thyroid
- -gland hypertrophy
- -increase renal excretion of iodine (need supplementation)
- -check TSH and free T4 to assess thyroid function in pregnacy
- Fetal Thyroid:
- -no organic iodide until 10 weeks
- -produce T3 and T4 by 11-12 weeks
- -mature levels of TSH, T4, free T4 by 12 weeks
- Crossing Placenta
- -iodide
- -T4
- -thyroid stimulating Abs
- -TRH
- -methimazole and PTU
- ***TSH does NOT cross
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Clinical Implications of Thyroid Changes
- Thyroid disorders → symptom mimicry
- -difficult to distinguish normal pregnancy from disease
- -lab changes (total T4 unreliable)
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Hyperthyroidism in Pregnancy
Radioactive iodine contraindicated
- Thyrotoxicosis → Thyroid Storm
- -high mortality rate if untreated
- -hyperthermia, tachycardia, perspiration, high output failure or dehydration
- -goal to lower HR, temperature, replace fluid losses, block secretion and synthesis of thyroid hormone
- Medical Treatment
- -PTU first line
- -methimazole (more concern about use in first trimester)
- ***both cross placenta so monitor monthly TFTs
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Hypothyroidism in Pregnancy
- Untreated hypothyroidism
- -increased risk for spontaneous abortion, low birth weight, stillbirth, decreased IQ
- -fetal thyroid deficiency during first and secondy trimester can lead to generalized developmental retardation
- -congenitaly hypothyroidism 1/4000
- Diagnosis:
- -elevated TSH
- -low free T4
- Treatment:
- -replace with levothyroxine and monitor monthly
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