L12.1 Preeclampsia

Question 1

3 different layers of placental vasculature

Answer 1

• Fetal
  
  • Fetal A & V in chorionic plate
• Fetal-maternal interface
  
  • Umbilical A & V bathed in maternal blood space
• Maternal
  
  • Endometrial (spiral) A & V

Question 2

Cytotrophoblast invasion

Answer 2

• Cytotrophoblast cells invade maternal spiral A
  
  • Differentiate from epithelial → endothelial
  • Large ↑SA → high flow and low resistance

Question 3

What happens with inadequte remodelling/invasion of the cytotrophoblasts?

Answer 3

• abnormal placental development and ↓placental perfusion

Question 4

Preeclampsia

Answer 4

• CVD characterised by hypertension >20 weeks gestation & excess serum protein levels in urine (>300mg)
• Other symptoms:
  
  • Generalised oedema
  • Symptoms apparent late in pregnancy
  • May progress into eclampsia → seizures and coma, death

Question 5

Why do mothers with PE still have be monitored after birth of baby?

Answer 5

• still have oedema and potential for eclampsia

Question 6

Impact of PE on babies

Answer 6

• Preeclamptic babies have low birth weight

Question 7

Causes of PE

Answer 7

• Unknown
• Begins at placenta and causes endothelial dysfuntion
  
  • → Hypoxic placenta and release toxics → endothelial damage → hypertensio

Question 8

Abnormal changes in spiral A in PE

Answer 8

• Invasion of spiral A is shallow
• Vascular SM is still relatively intact → still able to constrict → constrict BF even more and further ↓BF to placenta

Question 9

Treatment of PE

Answer 9

• No true cure/treatment
• Only “treatment” = deliver baby to take placenta out

Question 10

Soluble FIT1 (sFIT)

Answer 10

• Excess sFIT1 in preeclamptic women
• ↑sFIT1 → correlated with ↓ in serum VEGF
  
  • VEGF important for vascular relaxation and angiogenesis → to provide blood to placenta
• Treatment of rat with ↑sFIT-adenovirus → ↑MAP and caused proteineuria
• ↓Ability of renal microvessels to dilate → endothelial dysfunction
• A marker for PE

Question 11

Soluble endoglin(sENG)

Answer 11

• ↑ in PE women
• Still higher sFlT than sENG

Question 12

COMT1

Answer 12

• ↓ in PE women
• COMT1 → ↓2-ME serum levels
  
  • 2-ME responsible for converting hydroxyoestradiol
• Abnormalities in the uterine A
• Increase sFIT1 (decreases with 2-ME induction)

Question 13

Experiment showing importance of COMT1 (relating COMT1 to sFIT)

Answer 13

• sFIT levels elevated in COMT1 KO mice
• sFIT levels decrease after induction of 2-ME

Question 14

Relaxin and PE

Answer 14

• Relaxin used to widen pelvis
• ↓Relaxin → impaired vascular adaptations in pregnancy → ↑risk of developing PE

Question 15

Relaxin as a treatment

Answer 15

• Treatment with relaxin → restores normal pregnancy vasodilation in PE subcutaneous vessels
• ↓ sensitivity of vessels to vasoconstrictors and ↑ sensitivity to vasodilators
• ↓Stiffness in small renal and mesenteric A