Female Repro - Normal Pregnancy; Maternal adaptation, Hormones, Role of Placenta
What are the hormonal changes in preparation for labour and parturition?
1) Increase in fetal pituitary CRH and ACTH 2) Increase in fetal cortisol which - increases oestrogen which increases formation of oxytocin receptors on uterine muscle - inhibits progesterone, beginning contractions 3) Contractions feedback via mechanoreceptors, stimulating oxytocin secretion which increase contractions (positive feedback loop)
What are the cardiovascular changes during pregnancy?
1) Increased CO (30-50%) 2) Reduced systemic vascular resistance (decreased sensitivity to angiotensin II) 3) Increased HR (15-20 bpm) 4) Increased SV - from increased plasma volume
What are the haematological adaptations during pregnancy?
1) Increased erythropoietin (in response to progesterone, prolactin, HCG) 2) Increased clotting factors 3) Platelets unchanged (relative dilution) 4) Increased WBC (hormonal neutrophilia) 5) Increased blood volume - by 1.5L *Secondary physiological anaemia due to increased volume despite erythropoiesis
What are the respiratory adaptations in pregnancy?
1) Increased tidal volume, IRV 2) Respiratory rate same (or slight increase) 3) Decreased FRC, ERV, RV (due to upward shift of diaphragm) Overall: - TLC decreases slightly - tidal volume increase leads to state of relative hyperventilation - resultant respiratory alkalosis with renal compensation - FEV 1 unchanged
How does the maternal RAAS change during pregnancy?
1) Oestrogen stimulates hepatic synthesis of angiotensinogen 2) Oestrogen and progesterone stimulate secretion of renin 3) Angiotensin II increases - glomerulosa responses > aldosterone increases - maternal vasculature not responsive > no pressor effect 4) Aldosterone effect attenuated by antagonists - progesterone and oestrogen which reduce sodium resorption and relax smooth muscle
How do maternal thyroid hormones change during pregnancy?
1) TBG increases in response to oestrogen 2) Increased TBG lowers free T3 & T4 3) TSH increases in response 4) hCG increases, stimulating thyroid hormone production and suppressing TSH 5) T3 & T4 increases 6) Iodine decreases 7) TSH later increases when hCG decreases
How does blood flow in the uteroplacental circulation?
1) Uterine arteries bring maternal blood through low resistance vessels - blood squirts into intervillous space 2) Blood reaches the chorionic plate and then flows laterally and downwards, bathing the villi 3) Blood returns to maternal circulation through veins in decidual plate
What are the 4 main placental hormones?
1) hCG 2) Human chorionic somatolactotropin (hCS) - also called human placental lactogen (hPL) 3) Estrogen 4) Progesterone Other minor hormones - GnRH, CRH, Prolactin, GH, ACTH, IGF, PTH, Renin, ATII
Describe the structure of the umbilical cord
2 arteries 1 vein Arteries wrap around vein in a spiral fashion, helping to massage the blood along the vein with their pulsations Vessels are packed and protected by wharton's jelly
Describe marginal and velamentous insertion of the umbilical cord into the placenta
Normal - center of placenta Marginal - side/periphery of placenta Velamentous - cord vessels run in membranes before inserting into the placenta (not covered by wharton's jelly, vulnerable)
How does gas exchange occur at the placenta?
Passive diffusion of O2 and CO2
When is the greatest risk of teratogenicity?
Period of organogenesis 17 to 70 days post conception
What is placenta previa?
Placenta partially or wholly implants in the lower segment of the uterus
What is placenta succenturia?
Placenta with an accessory lobe, separated by membranes from the main placenta
What are the roles of oxytocin and prolactin in breastfeeding?
Prolactin induces change in mammary gland structure and promotes lactogenesis Oxytocin is stimulated by suckling (via paraventricular nuclei and supraoptic nucleus) Stimulates contraction of the myoepithelial cells surrounding the alveoli
Where is human chorionic gonadotropin produced?
Syncitiotrophoblast cells in the placenta
How does blood pressure change during pregnancy?
- Fall throughout 1st and 2nd trimester (systolic 5-10 mmHg, diastolic 10-15 mmHg) - Increase during 3rd trimester to non-pregnant levels
What is the impact of pregnancy on carbohydrate metabolism?
- Increased glucose utilisation, increased insulin secretion - Placenta produces HCS, progesterone, cortisol which act as insulin antagonists - Insulin resistance increases (to facilitate influx of nutrients to fetus?)
What are the GI changes in pregnancy?
1) Appetite increases - stimulated by progesterone, suppressed by estrogen 2) Reflux esophagitis - uterus increases intragastric pressure 3) Reduced GI motility caused by progesterone - constipation - aggravation of haemorrhoids
What are urinary changes during pregnancy?
1) Bladder - decreased tone caused by progesterone 2) Ureter - compressed by uterus and blood vessels - right more than left (physiological hydroureter and hydronephrosis) 3) Kidney - Increased renal blood flow due to increased CO and decreased resistance - Increased GFR, RAAS - Increased filtration of glucose (50% have glycosuria)
How does the maternal hypothalamic-pituitary-adrenal axis change during pregnancy?
1) CBG increases in response to oestrogen 2) ACTH levels increase in response to placental CRH 3) Cortisol increases in response to above 2 Fetal levels much lower, due to conversion by corticosteroid-11beta-dehydrogenase isoenzyme 2 in the placenta into cortisone
What are the functions of progesterone (5)?
1) Endometrial decidualisation 2) Inhibits myometrial contractility 3) Lowers prostaglandins 4) Inhibits immune response to fetus 5) Serves as substrate in fetal adrenals for glucocorticoids and mineralocorticoids
What are the immunological changes in pregnancy?
1) Enhancement of innate immunity; Suppression of adaptive immunity 2) Th2 stimulated (IL3, IL4, IL6, IL10) in favour of Th1 (IL2, TNFa) >>prevent rejection of semi-allogenic fetus)
What are postnatal changes in hormones?
1) Expulsion of placenta - many hormones decrease (oestrogen, progesterone) 2) Prolactin and oxytocin remain high to maintain breastfeeding 3) Oxytocin maintains contraction of uterine muscle, minimizing blood loss
What are the maternal pituitary endocrine changes in pregnancy?
1) Gonadotriphins - GnRH, FSH and LH suppressed from negative feedback 2) Prolactin increased - due to decreased dopamine suppression 3) Growth hormone - placental growth hormone increases, pituitary unchanged? 4) Corticotrophins - CRH from placenta stimulates ACTH from pituitary and placenta (also causes increase in MSH) 5) TSH - increases initially then falls in 1st trimester - 2nd and 3rd trimester increase again when hCG decreases 6) Oxytocin - wide variation. Increase in late pregnancy and labour 7) ADH - no change, remain low
What are the effects of progesterone on the respiratory system?
1) Hyperaemia 2) Decreased airway resistance (bronchiolar relaxation) 3) Increased mucous production
How are amino acids and fatty acids transferred at the placenta?
Active transport
What is a hemangiomata?
Benign tumour of the endothelial cells of the placental blood vessels
What is placenta circumvallate?
Chorionic plate too small Placenta implants more deeply into the decidua Membranes fold back on itself
What is placenta accreta?
Chorionic villi penetrate through the decidua and attach to myometrial layer of the uterus
What is placenta increta?
Chorionic villi penetrate through the decidua and penetrate the myometrial layer of the uterus
What is placenta percreta?
Chorionic villi penetrate through the myometrium and to the visceral peritonium May invade other organs eg. bladder
What is the function of hCS?
Closely related to prolactin and growth hormone Function not known Involved in insulin resistance
What hormones suppress T-cell mediated immune response toward the fetus?
Cortisol hCG Progesterone
What is the placental bed?
Decidua + myometrium
What are the sources of oestrogen production in early and late pregnancy?
Early - Maternal (ovary, adrenals, periphery) Late - Placenta Important in preparing the uterus for labour; stimulates growth of myometrium
What is hyperemesis gravidarium?
Excessive vomiting in early pregnancy Most associated with biochemical hyperthyroidism
How are glucose and lactate transferred at the placenta?
Facilitated diffusion via glut transporters
What is vasa previa?
Fetal vessels course through the membranes above the internal cervical os, unprotected by the placental tissue or umbilical cord Type 1 - velementous cord insertion Type 2 - vessels running between lobes
What are the skin changes in pregnancy?
Hyperpigmentation (eg. darker areola, linea nigra) Increased acne Increased varicose veins Hormones responsible: Progesterone, estrogens, CRH, ACTH, MSH
How do maternal parathyroid hormones change during pregnancy?
Increase in PTH Increase in calcitriol Doubling of intestinal calcium absorption Calcitonin unchanged
What are the changes in clotting factors in pregnancy?
Increased - factors VIII, IX, X - fibrinogen Decreased - fibrinolytics - Anti-thrombin - Protein S
What are the thyroid changes during pregnancy?
Increased hepatic synthesis of TBG Increased T3, T4 Relative iodine deficiency (increased requirements, increased urinary excretion)
What position are pregnant women advised to sleep in?
Lateral position When supine, uterus causes mechanical obstruction of the inferior vena cava and aorta
What is the function of hCG?
Maintenance of progesterone production from the corpus luteum until placenta can take over (6-8 weeks gestation)
What is a fetal cotyledon?
Unit of the placenta supplied by the vessels of a stem villus 15-28 in mature placenta
Which hormones share a subunit with hCG?
same alpha subunit TSH, FSH, LH
