Lecture 13 Pathological pregnancy

Question 1

What are the major CVS adaptions in the mother in normal pregnancy and when do they happen

Answer 1

1. Increased Cardiac output caused by
   - 10% increase in SV and -10-15% increase in pulse rate
   - 50% increase in blood volume
2. Reduced peripheral vascular resistance - to combat increased BP due to increased CO ^

These changes happen early in pregnancy from the missed menstrual period

Question 2

What are the 4 possible causes of the cardiovascular adaptions in pregnancy

Answer 2

1. Angiotensin 2: the effects of bp increase due to vasoconstriction blunted in normal pregnancy- possibly due to up regulation of inhibitory receptors
2. NO- acts locally in response to shear stress, upregulation of NO synthetase in some tissues increased in pregnancy to reduce pvr

Changes From 9-10 wks - where there are high concentrations:

3. Estrogen:
   - can reduce vascular resistance in reproductive tissues, make vessel walls more compliant by altering collagen ratio and increase NO synthetase expression

4.Progesterone: maybe vascular relaxation in uteroplacental circulation but not systemically

Question 3

Define pre-eclampsia

Answer 3

Multisystem disorder characterised by new onset hypertension 20+ weeks gest and involvement of one or more other organ systems and/or the fetus.

This commonly includes renal leading to proteinuria after hypertension,
but can be neurological, Fetal growth restriction, epigastric pain, stroke, pul oedema

Question 4

What is the pathogenesis of Pre-eclampsia

Answer 4

Failed maternal cvs adaption= less normal decrease of pvr in pregnancy

Exaggerated inflammatory response leading to vascular dysfunction.
This is triggered by something in the placenta as also seen in women with trophoblastic tumours

Question 5

What is the difference between late and early pre-eclampsia

Answer 5

Early: 20-34 wks onset at diagnosis, generally more severe but not always compared to

Late: 34+ wks onset.

Both considered to have different pathogenesis and different treatments but hasn’t been found yet

Question 6

What is the treatment of pre-eclampsia and the ongoing risks to women after pre-eclampsia

Answer 6

Delivery of the fetus- and placenta-to prevent progression of maternal signs and symptoms. Usually goes away but can be there post partum rarely.

Hypertension can be managed pharmacologically.

There is higher risk of CVD death- (eg. stroke) at an earlier age for women with pre-eclampsia, especially early onset, from 1->30 yrs after their delivery

Question 7

What is the difference between Small for Gestational Age (SGA) and FGR/IUGR - fetal/intra-uterine growth restriction

Answer 7

SGA are babies that have met their growth potential but are constitutionally small, generally <10th centile.

Harder to measure is the FGR and IUGR which are babies that have not met their growth potential due to underlying pathology (may be SGA or normal)

Can be seen in abnormal doppler waveforms in uterus and umbilical arteries but usually not detected until birth

Question 8

How do SGA/IUGR/FGR babies come about

Answer 8

The extravillous trophoblasts invasion into endometrium has started but it stops at the decidua-myometrial junction instead of going into 2/3 of myometrium.

Therefore there are less transformed spiral arteries, so the upstream arteries supplying the placenta are tonically active and constricted so there is restricted blood supply to the placenta/fetus- observed most in 3rd trimester.

Also poor development of the terminal villi.
Can lead to hypoxic/hyperoxic stress, placental inflammation, anti-angiogenic state, thrombo-occlusive damage

Question 9

What does SGA/IUGR/FGR placenta look like comparatively to normal baby

Answer 9

Around 20% thinner, 29% smaller placenta- less transfer from maternal to fetus

Decreased umbilical cord blood flow- blood flow through fetal circulation

In mild cases there is thinning and shorter vascular branches and if severe, then no. of branches reduces 36% as well

Question 10

What are the normal haemotological changes throughout pregnancy and what is the clinical application of this

• it doesn’t cause the CVS changes as there is cyclic changes in blood/plasma volume during the menstrual cycle about 10%

Answer 10

• Increased blood volume however plasma volume increases faster than cell mass, so overall
• Decreased haematocrit - until 30 wks where it remains stable.
• During delivery there is 500ml of blood lost per baby or 1 L in c section but the hypervolaemia means there doesn’t need to be vasoconstriction/ new production to compensate.
• Post partum there is continuing blood volume decline via diuresis thus haemotocrit returns to normal 6-7 wks post partum

therefore when doing blood tests, must compare to pregnant woman values not non pregnant woman

Question 11

What immune cells are present in the decidua that make it not immune privileged but still ok for baby with half paternal/maternal antigens

There is some evidence for the diminution of maternal immune response to some organisms in pregnancy- infections more severe like listeriosis, leprosy

Answer 11

70% of leukocytes: specialised uterine natural killer-like cell - good for cancer or viruses but generally need b cell antibodies to work well.

However there are almost no B cells, and only 10% are T cells

In pregnancy the T cells have a bias towards making more Th2 cytokines for antibody mediated responses rather than Th1 which is more cell mediated response which is seen in transplant rejection.

There is also increase of neutrophils population starting from the luteal phase which doesn’t drop. This peaks at 30 weeks then rises again at labour- innate immune response

Question 12

Does the maternal immune system reject sperm

Answer 12

No, repeated exposure to sperm helps to reduce pre eclampsia risk- tolerising maternal immune system to paternal/fetal antigens????

Seminal plasma has been found to be immunosuppressive and can reduce effectiveness of many components of the immune system in vitro