MS3 Medical Complications in Pregnancy

"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

• 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

• 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)

• 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

• 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

• 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

• 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

• 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)

• 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

• Decreased BP
• -DBP > SBP
• -nadir 24-32 weeks
• -normalized at term
• 

• Mediated by:
• -vasodilation (NO, Prostacyclin, estradiol)
• -Shunt

• Uterus
• -10 fold increase (from 50 to > 500 mL/min)
• -10-20% of CO
• 

• Breasts
• -increased flow

• Renal
• -50-80% increase
• -% of CO stable
• -for waste excretion

• Skin
• -heat dissipation
• -mucous congestion

• Pulmonary
• -vascular markings on CSR

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

• 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

-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

• 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

• 
• 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

• 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

-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

• -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

Hyperventilation causes alkalosis

Fetus can handle low PO2 due to HbF

Fetal umbilical vein contains oxygenated blood

• 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

• 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

• V/Q scan
• -safe

• CT scan
• -dose and timing
• -first trimester

Angiogram

Lower extremity U/S

D-dimer

• 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

• 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

• Thyroid disorders → symptom mimicry
• -difficult to distinguish normal pregnancy from disease
• -lab changes (total T4 unreliable)

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

• 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