Lecture 13: The Placenta and pregnancy (III) Flashcards
Describe the structure of Human Chorionic Gonadotrophins
Describe what produces the hCG
- Two chain hormone that shares it’s αchain with TSH, LH and FSH
- The hormones all have a unique βchain
- βhCGis produced exclusively by the syncytiotrophoblast of the p_reimplantation blastocyst_ and placenta
- βhCGis detectable in the maternal blood/urine within days of implantation
βhCGis produced exclusively by the ________of the _______and ______
βhCGis produced exclusively by the syncytiotrophoblast of the preimplantation blastocyst and placenta
We can use hCG clinically as an indicator of….
Indicator of health of the pregnancy
What are the functions of hCG?
- •hCG binds to the LH/hCG receptor and thus transmits similar signals to LH. (the half life is longer than LH)
-
•Luteal support:
- •hCG has strong leutotrophic properties and is important in _stimulating the production of progesterone and oestroge_n by the ovary during the first 6-8 weeks of pregnancy.
- •stops regression of the corpus luteum.
- •The CL doubles in size about a month into pregnancy under the influence of hCG
- •After this time point the placenta takes over from the ovary as the major source of progesterone.
- •hCG is basically responsible for preventing the uterus returning to its normal cyclic pattern by causing the CL to continue to secrete Prog and oestrogen.
- •These hormones prevent menstruation and maintain the endometrium in a decidualised form.
hCG binds to the _______receptor and thus _______
hCG binds to the LH/hCG receptor and thus transmits similar signals to LH.
Women with multiple pregnancies have _______ levels of HcG
Women with multiple pregnancies have increased levels of hcG
This is because of the increased amount of syncytiotrophoblast in twin pregnancy
The importance of hCG in maintaining pregnancy can be seen int eh use of this hormone as a target for _______
Contraceptive vaccines
Aside from pregnancy, high levels of hCG are found in _______
Trophoblastic tumours. Choriocarcinoma and hydatidiform mole, and also in testicular cancers
Progesterone is synthesised by ………
Synctiotrophoblast of the placenta.
Shown by production by moles and choriocarcinomas
Removal of the ovaries does not compromise human pregnancy after ________
6-8 weeks of gestation (may be required due to a tumour)
Syntytiotrophoblast expresses various receptors to __________
Assist LDL uptake (when we make steroids, we make them from inorganic acetate, but trophoblasts cannot synthesise progesterone from acetate).
Because progesterone is crucial to pregnancy, the placenta is laden with receptors that carry LDL cholesterol from mum’s blood into the placenta.
When we make steroids, we make them from inorganic acetate, but trophoblasts cannot synthesise progesterone from acetate. Therefore …….
Therefore instead, Syntytiotrophoblast expresses various receptors to Assist LDL uptake
Because progesterone is crucial to pregnancy, the placenta is laden with receptors that carry LDL cholesterol from mum’s blood into the placenta.
What is the function of progesterone?
Progesterone maintains uterine quiescence (state of inactivity)
Along with oestrogens, progesterone converts the uterine environment to one that is conducive to pregnancy
Progestrone receptors are expressed by both glands and stromal cells in the endometrium/decidua
Prog induces formation of the decidua. Decidua may just be specialised tissue that is important for providing nutrients prior to tapping the maternal blood supply but
The decidua is not essential for implantation as is demonstrated by ectopic pregnancy
It is postulated that decidua may be important for regulating the extent of implantation. If this is correct it is important to maintain the decidua throughout pregnancy
Progestrone receptors are expressed by ________
Progestrone receptors are expressed by both glands and stromal cells in the endometrium/decidua
Prog induces formation of the _______.
Decidua. Decidua may just be specialised tissue that is important for providing nutrients prior to tapping the maternal blood supply but
The decidua is not essential for implantation as is demonstrated by ectopic pregnancy
It is postulated that decidua may be important for regulating the extent of implantation. If this is correct it is important to maintain the decidua throughout pregnancy
The decidua is/is not essential for implantation as is demonstrated by _______.
Decidua may be important for…..
The decidua is not essential for implantation as is demonstrated by ectopic pregnancy
It is postulated that decidua may be important for regulating the extent of implantation. If this is correct it is important to maintain the decidua throughout pregnancy
Can human placenta produce oestrogen de novo (“new”?
No, human placenta has no 17 alpha hydroxylase (convert progesterones to androgens)and cannot produce oestrogen de novo.
But placenta can aromatise testosterone, androstenedione and dehydroepiandrostene to oestrone and oestradiol
If the fetus cannot produce oestrogen de novo, what does it do to?
human placenta has _no 17 alpha hydroxylas_e (convert progesterones to androgens)and cannot produce oestrogen de novo.
Fetal adrenals can produce androstenedione and dehydroepiandrostene but can not convert them to oestrogens.
But placenta can then a_romatise testosterone_, androstenedione and dehydroepiandrostene to oestrone and oestradiol
Anencephalic pregnancies (in which the adrenals are usually atrophic) usually have low levels of oestrogens
What are the maternal adaptations during pregnancy
Changes occur in
•Most systems of the body including
•The maternal cardiovascular system
•The haematological system
•The maternal immune system
•The genital system
_____% of progesterone and estrogen produced in the placenta are shuffled into the maternal blood not the fetal blood
85-90%
Preecalmpsia is more common in ______
First pregnancies/paternities
First pregnancies tend to be more prone to complications of mal-adaptation than subsequent gestations
What is Preeclampsia?
Preeclampsia –dangerously elevated maternal blood pressure accompanied by protein in the urine
- 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.
- loss of the normal m_aternal peripheral vascular resistance_ (normally resistance relaxes)
Describe the Cardiovascular adaptations in normal pregnancy vs during preeclampsia
Most important changes are
- Increased cardiac output
- Caused by a 10% increase in stroke volume and 10-15% increase in pulse rate.
- Reduced peripheral vascular resistance
Pregnancies complicated by preeclampsia are characterised by higher than “normal” peripheral resistance.
Describe the role of Oestrogen on CV changes
- Can reduce vascular resistance mainly in reproductive tissues
- Can alter the ratio of type I /type III collagen in the vessel wall
- High levels of oestrogen a_re not reached until 9 weeks_ when fetal adrenals induce synthesis.
Describe the role of Progesterone on CV changes
Describe Angiotension II and CV changes
- Angiotensin II (AII) is basically a vasoconstrictor which causes the arterioles to contract and thereby increases BP –its levels increase in pregnancy
- The uteroplacentalunit produces large amounts of the RAS
- The effects of AII appear to be blunted in normal pregnancy
- possibly due to receptor changes
Describe the role of NO and CV changes
- NO is produced by vascular endothelial cells by nitric oxide synthetase in response to the shear stress of blood flowing over the vessel surface.
- Nitric oxide has a ½ life of 6 seconds and causes arterial wall relaxation and dilation.
- The activity of nitric oxide synthetasein some tissues is increased in pregnancy.
Describe the Haematolgical changes with pregnancy (changes in blood)
1) Increased blood volume
2) Plasma volume and blood volume both increase in human pregnancy but at different rates.
3) Thus the _haematocrit (blood cell volcume) decline_s in pregnancy as plasma volume increases at a higher rate than cell mass
4) Plasma volume increases by 1250 mls by 30 weeks and thereafter remains stable.
When you’re checking a blood test of a pregnant woman….always……..
Check the values against the “normal” values of a pregnant woman
Plasma volume and blood volume both increase in human pregnancy but at different rates.
During delivery there is __________ (Haemotological Changes)
During delivery there is substantial blood loss 500mls for a singleton vaginal delivery 1 litre for twins and about 1 litre during caesarean section.
Thus, the heamatocritslowly returns to normal postpartum.
What drives the CV changes in normal pregnancy?
Lots of possibilities but we are not certain
But if this doesn’t occur properly, can result in preeclampsia
Describe the Immune responses to pregnancy
- There is some evidence for a diminution of the maternal immune response to some organisms in pregnancy.
- Some infections if first encountered in pregnancy may be more severe e.g. leprocy, colds
-
White cell count rises due to expansion of the neutrophil population, which commences in the leutealphase of the cycle and does not drop with pregnancy.
- Neutrophil counts peak at 30 weeks then rise again at the time of labour
- Neurtrophil does not result in transplant rejection
-
Lymphocyte counts do not alter greatly in pregnancy but there is believe to be a bias in the type of T helper (CD4) cells and the cytokines they produce with a tilt in the balance toward Th2 cytokines
- Th1 cytokines drive the immune system towards a c_ell mediated_ (cytotoxicT cell, ietransplant rejection) response
- Th2 cytokines drive the immune system towards an a_ntibody mediated_ response.
_______ appears to be beneficial protecting against pre-eclampsia.
Repeated exposure to sperm appears to be beneficial protecting against pre-eclampsia.
(with the sperm donor. New partner- reset risk)
Describe the white cells in the decidua
•The decidua contains:
- almost no B cells (no antibody production)
- about 10% of the leuocytes in the decidua are T cells
- _70% o_f the leucocytes are specialised uterine natural killer-like cells. (incapable of killing via antibodies)
Majority of the leucocytes in the decidua are __________
70% of the leucocytes are specialised uterine natural killer-like cells. (incapable of killing via antibodies)
What are recurrent miscarriages?
Three or more consecutive pregnancy losses.
With each miscarriage, the chances of furture pregnancy decreases
Compare mean CD3 T cell density in the placental bed of Recurrent Miscarraige vs normal pregnancy
Recurrent Miscarraige: higher decidual T cell
Describe changes in skin during pregnancy
- Blood flow to the skin is increased in pregnancy (reduce temp)
- Pregnant women often have warm and clammy hands
- Flow to the hands is increased 6-7 fold
- Flow to the feet is also increased
- These areas generally indicate raised flow to other skin regions.
- There are _pigmentation changes in some area of skin nipple_s and areola
- There is also development of a lineanigra
- Chloasmamay develop mainly in the neck and face -lost or regress after pregnancy (usually)
- These pigmentation changes are due to an increased secretion of melanocyte stimulating hormone which is markedly elevated from the second month of pregnancy.
- Suntans develop well in pregnancy
In the latter part of pregnancy approximately 50% of pregnant women develop ______
n the latter part of pregnancy approximately 50% of pregnant women develop Striae Gravidarum-reddish slightly depressed streaks –in the skin of the abdomen, thighs and breasts.
