Lecture 18: Physiology of pregnancy 1 Flashcards
Hormone 1: Human Chorionic Gonadotrophin (hCG)
WHat is it, where is it produced and when can you detect it?
-
2 Chain hormone that shares it’s a chain with TSH, LH and FSH
- The hormones all have a unique B chain
-
BhCG is produced only by:
- syncytiotrophoblast of the placenta
- trophectoderm of the preimplantation blastocyst cells that will become the embryo
- BhCG is detectable in the maternal blood/urin within days of implanatation
BhCG as a diagnostic tool?
Used to confirm pregnancy via detection of BhCG in urine dipsticks or blood samples.
BhCG secretion increased rapidly in the 1st weeks of pregnancy and peaks at 100,000units/ml at 10 weeks gestation
Post 10 weeks: levels drop off to ~20,000units/ml
- First line: control line (shows testing unit is functional)*
- Second line: confirms pregnancy*
What’s the Function of hCG during the first 6-8weeks of preganacy?
- Binds to the LH/hCG receptor (shared) and transmits a similar signal to LH
- Luteal Support
- hCG has strong leutotrophic properties: important in stimulating progesterone and oestrogen production by the ovary in the first 6-8weeks of pregnancy
- Stops regression of the corpus luteum (tells mum she is pregnant)
- THe Corpus Luteum doubles in size about a month into pregnancy under the influence of hCG
What’s the function of hCG after the first 6-8weeks of preganacy?
Around now the placenta takes over from the ovary as the major source of progesterone.
- Now hCG main function: stop the uterus from returning to its normal cyclic pattern.
- Does this by stimulating Corpus Luteum to continue secreting progesterone/eostrogen
- These prevent menstruation and maintain the endometrium in a decidualised form
- Women with ovarian cancer can have oophorectomy past this point and maintain pregnancy as ovaries are no longer needed
What type of tumours produce high levels of hCG?
Trophoblastic tumours.
- Choriocarcinoma (cancer of uterus) and hydatidiform mole (are mass or growth that forms inside the womb (uterus) at the beginning of a pregnancy)
- also some testicular tumours
Why is hCG so important in pregnancies of male fetuses?
As it is so similar to LH, it produces LH-like activity.
It stimulates synthesis by leydig cells of the fetus testis → stimulates testosterone → drives sexual differentiation
At this early point in development, the pituitary (and therefore LH) have nott formed so you need a replacement.
THis is crtitical for phenotypic sexual differation of males?
Hormone 2: Progesterone
What is it synthesised from?
Synthesised by the
Syncytiotrophoblast of Placenta: shown by choriocarcinoma and hydatidiform moles produce progesterone by themselves
But as trophoblasts can’t convert Acetate → Cholesterols, it instead uses LDL-cholesterol derived from maternal circulation.
The Syncytiotrophpblasts expresses various receptors to assist this LDL uptake.
How is it that women with high hCG levels can get hyperthyroidism?
A consequence of the 4 hormones LH, FSH, TSH and hCG being so structurally similar is that there is cross reactivity.
SO hCG can lead to stimulation ofthe TSH receptor (or via the LH receptor) in the thyroid.
So choriocarcinoma and hydatidiform moles which produce hCG at very high levels can become hypethyroid
Is the fetus required for progesterone production by the placenta, and why?
No because
- Ligation of the cord doesn’t cause an immediate drop in circulating progesterone levels
-
Removal of the ovaries (with it’s CL) doesn’t compromise human pregnancy after 6 weeks gestation
- Suggests placenta is now producing adequate progetsterone to maintain the pregnancy
Why does there need to be collaberation between the fetus and the placenta in order to produce oestrogens?
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Placenta can’t produce 17a hydrolyase enzyme so can’t (progesterone → Androgens)
- hydratidiform moles and choriocarcinomas can’t produced oestrogen, only progesterone
- Placenta can aromatise Testosterone/androstenedione/dehydroepiandrostene → estrogen/oestrodial
- Fetal adrenals can P4 → Androgens (androstenedione + dehydroepiandrostene) but can’t convert them to oestrogens
- So progesterone gets shunted to adrenalsand liver (requires live fetal circulation) and then back to placenta to be aromatised
**this is why Anencephalic pregnancies (atrophic adrenals) there’s low levels of oestrogens
What are the functions of Progesterone during pregnancy?
- Maintains uterine quiescence
- Converts (along with oestrogens which primes expression of the P4 receptors) the uterine environment → environment conductive of pregnancy
- P4 receptors are expressed by both glands and stromal cells in the endometrium/decidua
- Induces formation of the Decidua
What are the Cardiovascular Maternal Adaptations during pregnancy?
- Increased Cardiac Output: Caused by
- 10% increase in SV
- 10-15% increase in pulse rate
- In normal person this would increase BP, which is compensated for by…..
- Reduced Peripheral Vascular resistance
Preeclamptic pregnancies are characterised by higher then ‘normal’ peripheral resistance
Hormone 3: Oestrogens
What are they produced by and what is required for this, how do the levels change through preganancy
- Produced in large quantities by the feto-placental unit, requires
- A live fetus (unlike P4)
- Function Fetal Adrenals
- Intact Feto-placental circulation
- A functioning placenta
- There’s a 1000-fold increase in oestorgens in pregnancy.
*
What is Preeclampsia?
Elevated maternal BP after 20 weeks gestation. Often accompanied by proteinuria.
Caused from multi-organ dysfunction (brain > visual disturbia, impaired liver function, renal insufficiency, pulmonary thrombocytopenia)
- Affects most maternal organs
- Triggered from something from the placenta (only occurs in pregnant women)
- An exaggerated inflammatory response → vascular dysfunction
- Falure of the normal vascular adaptation to pregnancy
- Loss of the normal maternal peripheral vascular resistance relaxation: see Hypertension weeks before clinical diagnosis
