Lecture 17: Physiology of Pregnancy Flashcards
describe the relationship between the foetus and mother;
Essentially a parasite (genetically foreign) and wants as many nutrients as possible to grow
What does the placenta produce?
Many hormones and growth factors
What may create immunological tolerance e to the foetus?
The placenta may induce immunological tolerance
Give an overview of the interelationship between the mother and foetus;
- Without the health of the mother the foetus wont make it.
- Mums CV and immune system adapt to support pregnancy
What are the maternal adaptations to pregnancy?
Changes in most systems of the body, including;
- The maternal cardiovascular system
- The haematological system
- The genital system
Does the number of pregnancies influence maternal adaptation?
First pregnancies tend to be more prone to complications of mal-adaptation than subsequent adaptations
Describe the length of time the adaptations occur for?
“9” months of pregnancy, more like 40 weeks
profound changes take place in the maternal physiology to allow gestation to proceed for nine months
What are the two greatest changes of the maternal CV system?
Increased cardiac output
Reduced peripheral resistance
How is increased cardiac output achieved?
10% increase in SV and 10-15% increase HR
Describe how peripheral resistance is reduced;
- Increased hormone levels (estrogen, prostaglandins) cause vasodilation, thus decreased vascular resistance
- Decreased peripheral resistance causes a small decrease in systolic blood pressure and a more marked decrease in diastolic blood pressure.
When do CV changes occur in pregnancy?
CV changes begin very early in pregnancy, reach their peak during the second trimester and then remain relatively constant until delivery.
Describe the changes in blood flow to the uterus in pregnancy?
- Uterine vessels become dilated, blood flow increases from 45mL/min to 750mL/min
- These cells must increase drastically in length and width (radial artery 200% increase in diam) == cellular proliferation
Describe the vasculature of the placenta;
The placenta is fed by the uterine arteries -> arcuate -> radial -> spiral arteries
Why do these vascular changes occur?
Because of changes in the progesterone and estrogen levels
Describe how progesterone causes vascular changes;
Firstly is produced by the corpus luteum and then by the placenta;
- induces vascular relaxation in the uteroplacental circulation but does not appear to have a systemic affect
Describe how estrogens cause vascular changes;
Estrogen;
- Reduces vascular resistance mainly in reproductive tissues
- Alters the ratio of type 1/3 collagen in the vessel wall
- Increases angiontensinogen by synthesis in the liver, leading to increased serum levels of ANG 2
If ANG2 is a vasoconstrictor then how come it is released in pregnancy and why does it not cause hypertension?
There is an 8 fold increase in ANG2 to increase electrolyte re-absoprtion and blood volume
but
The affects of ANG2 on vasoconstriction appear to be blunted in normal pregnancy.
= increased vasodilator response
What are prostenoids and how do they change in pregnancy?
Prostenoids/prostaglandins are derived from arachidonic acid.
- PGI2 (vasodilator) increases 5 fold by term
Do all prostaglandins cause vasodilation?
No some can cause vasoconstriction but in pregnancy this equilibrium favours vasodilation and of note there is no increase in TXA activity.
Whats the vasodilators of pregnancy?
Prostaglandins
Nitric Oxide
Describe NO
NO is produced by vascular endothelial cells in response to shear stress of blood flowing over the vessel walls
NO acts locally
Has a half life of 6 seconds
Causes arterial wall relaxation and dilation
How does NO change in pregnancy?
- During pregnancy some tissues has enhanced Nitric Oxide Synthase activity
- NO contributes to maternal systemic vasodilation and reduced vascular reactivity (i.e to SNS) during normal pregnancy
- NO has localised uterine actions
What are the NO localised uterine actions?
- Uterus has NOS activity, which decreases at the end of gestation
- Uterine arteries have increased endothelial NOS activity
- NO is also produced by EVTs - may hep invasion (of spiral art.) or contribute to vasodilatory environment
Describe the heamotological changes of pregnancy;
- Increased BV
- Increased plasma volume
(these occur at different rates) - Haematocrit declines in pregnancy as plasma volume increases faster than cell mass (but RBC does increase in mass)
- Plasma volume increases by 1250mL by 30 weeks then becomes stable.
How is there changes in blood and plasma volume in pregnancy?
- Renin and aldosterone progressively increase 8 fold in pregnancy
- Retain noromotension by vasodilator response
- Vascular compliance
When else do females plasma/BV change?
During the regular menstrual cycle
Describe plasma volume change over time
- By 8-10 weeks of gestation, plasma volume inc. 10% (similar to mesntural cycle)
- by 10 weeks of gestation there are significant CV adaptations already, Plasma expansion occurs after this, thus plasma volume doesnt cause the CV changes
What are pregnant women at risk of developing in relation to CV changes?
- Pre-eclampsia (hypertension +proturia)
- Anemia (B/C extra iron required by the foetus, placenta and the increased in RBC mass.
What is the point of the CV adaptations?
- CV adaptations mean that uterine blood flow increases from 50ml?min to 700-800mL/min = placenta/foetus can exchange more nutrients and gasses with the mother, ensuring healthy foetal growth.
How do CV adaptations help during birth?
Birth is traumatic! Th Cv adaptations help protect the mother from risks of delivery such as haemorrhage
Describe the haemodynamic changes at birth
- 0.5L vaginal singleton borth
- 1L vaginal twins
- 1L c section
How does the pregnant women respond to blood loss in child birth?
Non-pregnant women would vasoconstrict and produce new blood.
Pregnant women are hypervolemic thus modifying the response and they do not respond to this blood loss. (there is continuing blood volume decline by diuresis and a slow loss of red cells with time post partum)
Haematocrit slowly returns to normal post partum
How does the foetus pose an immunological risk?
- It is considered foreign by the maternal immune system
- The placenta is in intimate contact with maternal blood and high numbers of immune cells in the decidua
Why is the foetus not rejected?
- Placenta hides itself from immune system
- Trophoblasts alter the expression of cytokines from immune cells in order to dampen down the maternal immune response.
Describe how the placenta hides itself;
Trophoblasts do not express class 1 or 2 MHCs. = hiding it. (HLA-A,B)
Trophoblasts express a combination of HLA-C, G and E MHC molecules which actively help the placenta avoid immune attack
Describe HLA-G function;
HLA-G can interact with receptors on cytotoxic T lymphocytes and natural killer cells, inhibiting their ability to induce cell lysis.
Describe how shedding contributes to maternal tolerance
Synctiotrophoblasts are an epithelial layer that constant shed into maternal circulation
- Trophoblast debris interact with endothelial cells and macrophages in maternal circulation
= may play a role in immunological tolerance of the placenta / foetus
What happens when maternal CV adaptation goes wrong?
Pre-eclampsia ; hypertension + proterurea
Describe the affects of pre-eclampsia
- Affects most maternal organs
- Found only in pregnancy
- Triggered by something from the placenta
- An exaggerated inflammatory response leading to vascular dysfunction
- Failure of the normal vascular adaptation to pregnancy
More common in first pregnancies
What can cause pre-eclampsia
Pre-eclampsia is the result of defective maternal adaptation of the CV and or immune systems to pregnancy
- Defective uterine sprial art. remodelling
- Release of pro-inflam trophoblast debris (instead of adaptive cytokines)
- Inability of the maternal CV system to cope with the increased inflammatory profile.
- Multifactorial disease
Describe RAAS in pre-eclampsia;
Pre-eclamptic women have;
- Lower RAS components
- But increased ANG 2 sensitivity in their adrenal cortex and vascular system
What happens to vasodilators in pre-eclampsia?
- Reduced PGI2 by 13-14 weeks
- TXA rises from 21 weeks leading to hypertensive imbalance
- Associated with AMDA dysregulation (It inhibits NOS)
- Blockade of NO synthesis induces pre-eclampsia.
Describe hCG structure;
2 Chain
Shares its alpha chain with FSH and LH
The hormones all have a unique beta chain
What produces hCG?
hCG is exclusively produced by the trophectoderm on the preimplantation blastocyst and syncytriotrophoblast of the placenta
Women with multiple pregnancies will experiences even higher levels of hCG, as the amount of syncytiotrophoblast is increased
When is hCG detectable?
hCG is detectable within the blood/urine within days of implantation
bhCG is used for detecting (as alpha chain is shared)
Describe hCG levels on a timescale basis
bhCG secretion increases rapidly in the first weeks of pregnancy until 10 weeks of gestation whereafter it drops off.
How does hCG influence the corpus luteum?
- hCG plays a critical role in the development of pregnancy by preventing regression of the corpus luteum
- Thus progesterone secretion by the corpus luteum maintains the endometrium’s receptivity for implantation
Describe the action of hCG on the corpus luteum;
hCG binds to the LH receptor and thus transmits similar signals to LH =
- Corpus luteum doubles in size by 4 weeks
- Also causes ovarian release of estrogen and progesterone during first 6-8 weeks
- At this point placenta takes over as major source of progesterone
Describe hCG and decidua interplay
hCG is basically responsible for preventing the uterus returning to its normal cyclic pattern by causing the corpus luteum to continue secreting progesterone and estrogen
Thus these hormones prevent menstruation and maintain the endometrium in a decidualised form
How may hCG influence uterine vascular remodelling?
hCG may play an important role in uterine remodelling right from the time of implantation
- angiogenic factor
- stimulates vasodilation and vascular permeability
Where else are high levels of hCG found?
Trophoblastic tumors
- choriocarcinoma
- testicular tumor
How can hCG be used as a contraceptive target?
The importance of hCG in maintaining pregnancy can be seen in the use of this hormone as a target for contraceptive vaccines.
Phase 1 and 2 clinical trials indicated safe, efficacy and reversibility for a beta hCG vaccine
What are the limitations of the bhCG vaccine?
- The vaccine did not produce antibodies in all women
- Antibodies were short lasting
- 3 months to produce antibodies
- unknown long term effects
Describe the uterus
non-pregnant = almost solid
70g
10mls
Pregnant uterus is thin walled and muscular with a 5L cavity (can go up to 20L) and weighs 1100g
Describe uterine growth;
The initial growth of the uterus is at least partially under the control of estrogen
- Growth is largely due to stretching of existing cells rather than proliferation of cells
- 5cm in length when non-pregnant, 40-60cm at term
Describe the cervix and pregnancy;
Cervix softens and glands proliferate to occupy approximately 50% of the mass of the cervix.
Cervix is blocked by mucous plug during pregnancy (prevents infection)
How does cervical composition change with pregnancy?
80% collagen when non-pregnant
Towards term collagen content of the cervix decreases while its elastin is unchanged but glycosaminoglycans and water increase
Incompetent cervix is associated with repeated miscarriage
How does the abdominal wall /skin change in pregnancy?
increased blood flow to skin
Flow to hands increases 6-7 fold
Flow to feet also increases
How does the abdomen change and skin pigment?
Skin,nipple and areola change pigment with pregnancy, (increased malanocyte sitmulating hormone) easier to tan.
Development of linear nigra
Facial pigmentation (regress post preg)
What can happen to womens abdomens in pregnancy?
IN later pregnancy 50% of women develop striae Gravidarum (reddish streaks formed on the skin, abdomen and thighs, breasts)
Due to overstretching of the skin, elastic fibres may rupture together with small blood vessels
