Physiology of pregnancy 2 Flashcards
Implantation of blastocyst day 7
- Interact/ bind via cell surface glycoproteins -> adhesion
- Blastocyst invades uterine wall (=endometrium)
-> 2 populations/ layers of throboplast cells (of blastocyst) develop/ further differentiate into the embryonic portion of placenta: - (outer) syncytiotrophoblast: invades the endometrium- forms cavities/spaces called lacunae: filled with maternal blood -> will form maternal-fetal blood barrier
- (inner) cytotrophoblast: remains near embryonic tissues- branches called chorionic villi protrude into lacunae
! rarely a fertilised egg remains on the fallopian tube and embeds in the tube wall= ectopic pregnancy
Implantation of blastocyst day 8-12- invades uterine wall
Throboplast population is a single, multinucleated cell mass (=syncytium)
- No cell boundaries, formed by the fusion of throboplast cells
- Implantation is complete by day 12 (26 day of cycle)- the syncytiotrophoblast completely surrounds embryo.
Formation of placenta 14-20 day- intermediate state of placenta formation
Placenta: organ of gas, nutrient and waste exchange between the embryo and mother
As maternal blood vessels are encountered by syncytiotrophoblast- lacunae/ sinuses form and are filled with maternal blood
formation of placenta at 1 month
Cytotrophoblast cords surround the syncytiothroboplast and lacunae & embryonic blood vessels enter the cord
Branches (chorionic villi) sprout from the cords- protrude into lacunae
endometrial changes after implantation- stem-villus stage
Decidua: endometrium of the pregnant uterus
Uterine mucose (decidual layer/ decidua) reacts to implantation by undergoing decidual reaction:
1. Cellular changes
- Endometrial stromal cells enlarge – transform into decidual cells
-> Are filled with glycogen- provide nourishment for embryo to grow (until placenta becomes vascularised and takes over)
2. Vascular changes
- Implantation results in breakdown/ erosion of maternal spiral blood vessels (throbopöast secretes digestive enzymes)
-> Lacunae ( blood filled spaces) between chorionic villi
the mature placenta at the end of the first trimester
- Chorionic villi become vascularised by fetal vessels(capillaries ehich carry fetal blood in close proximity to maternal blood (BUT DO NOT MIX)
- Dialysis pattern of blood flow is established
mature placenta and fetus: maternal and fetal blood dont mix
Entire embryonic structure facing maternla tissue is called chorion (syncytiotrophoblast + basement membrane)
In the mature placenta (end of first trimester):
- Cytotrophoblast disappears -> fetal blood supply is separated from the maternal by fetal capillary wall, basement membrane, and a thin layer of syncytiotrophoblast
enlargeemnt of uterus during pregnancy
- Most morphological changes occur in embryonic period of development
- growth is a major feature of the fetal period
-> Fetus grows from around 3cm and 2,5 g to around 50cm and 3300g at term
- growth is a major feature of the fetal period
Placenta previa
Implantation occurs normally in the fundus area of the uterus
Placenta previa: condition that occurs when the blastocyst implants near the cervix:
- During placental growth the placenta may extend partially or completely across the internal cervical opening- may prevent vaginal birth
- As fetus and placenta grow (uterus stretches) the region of the placenta over cervical opening may tear = haemorrhaging may occur
-> Can result in miscarriage and place the mother in danger
Prenatal development- 3 stages
- Germinal period: first 2 weeks of development during formation of primitive germ layers (e.g. mesoderm).
- Begins at fertilisation and ends at 14 days post. - Embryonic period: weeks 3 to 8, organ systems develop.
Occurs during days 14-56 days after fertilisation:
- Major organ systems form.
- Developing human is called an embryo. - Fetal period: last 30 weeks, organ systems grow and mature.
Extends from 56 days after fertilisation to birth:
- Organ systems grow and mature.
- Developing human is called a fetus.
Role of placenta: organ of exchange
For a substance ( gas, nutrients, waste) to be exchanged between the maternal and fetal circulations it must diffuse between the:
- Syncytiotrophoblast
- Fetal capillary endothelial layer (very thin: single layer of cells on a basement membrane)
Recap: rate & extent of diffusion across a cellular barrier depends on:
- Nature/ thickness of barrier
- Available surface area
- Concentration graxients
-> Placental barrier is quite impermeable
Placenta: diffusion of dissolved gases: Ficks law
Fick’s law applies to all systems of gas exchange: whether in air or water, diffusion rates of respiratory gases depend on their partial pressure gradients and some other factors:
Fick’s law: rate at which a gas diffuses between two locations (Q), depends on:
- Diffusion coefficient (D); incorporates temp., diffusing substance, medium;
- Area (A) over which the gas is diffusing -> enormous surface area, which is maximized by extensive branching of fetal capillaries within villi.
- Difference between the gas partial pressures (P1 – P2) at the two locations -> maximized by high perfusion/blood flow rate (dialysis arrangement of placental blood flow helps maximise solute concentration gradients).
- Distance (L) between the two locations (i.e. path length) -> not great (placental barrier is rather impermeable).
Placenta blood flow in full-term fetus- Dialysis pattern of blood flow
- Fetal blood capillaries (in chorionic /placenta villi): total blood volume of about 45 ml, exchanged about 8x each minute smaller volume than maternal blood spaces, but has a greater turnover.
- Overall: optimises condition for passive exchange of solutes by maximising their concentration gradients.
- Intervillous space (pool of maternal blood): total blood volume of about 250 ml; exchanged ~2x each minute well-mixed blood, decent turnover:
-> Blood enters at a high pressure (good turbulence/mixing).
Placental gas exchange occurs by diffusion: partial pressure gradients (Pgas)
Oxygen (O2) diffuses passively from maternal to fetal side of the placenta; carbon dioxide (CO2) diffuses in opposite direction.
Blood is quite deoxygenated and hypercapnic: i.e. has abnormally high level of CO2 in arterial blood (PaCO2 >45 mm Hg; 6 kPa).
Fetal blood is not in equilibrium with maternal blood – why..?
(1) Not all maternal blood is in contact with chorionic villi.
(1) Placenta itself uses 20% of the maternal O2 supplied.
Satisfying the O2 demand of the fetus: example of an adaptation
The fetus depends on the placenta for gas exchange as its lungs are not yet functional (alveoli are almost collapsed and fluid-filled…).
-> Adaptations enable transfer of O2 to fetal tissues to be maximised:
Recap: fetal blood has a higher affinity for O2 than adult blood:
(1) Fetal blood has a higher haemoglobin (Hb) concentration helps it carry more O2 (vs. adult).
(2) Fetal Hb has a higher O2 affinity has two γ-polypeptide chains (instead of β chains, as in adult Hb).
Fetal O2 dissociation curve: shifted to left
Affinity & P50 are inversely related: as P50 ↑, O2 affinity ↓
- Umbilical artery: PaO2 = 16 mm Hg fetal Hb unloads O2 to tissues
- Umbilical vein: PO2 = 29 mm Hg maternal Hb unloads O2 to fetal Hb.
- Fetal aorta: PaO2 = 20 mm Hg (LOW!); even so still 60-65% saturated with O2!
-> Shift to left: higher degree of saturation of fetal Hb for a given PO2.
Placental exchange beyond O2
The fetus depends on the placenta for gas exchange, but also for nutrition (e.g. glucose) and waste disposal (e.g. CO2, urea…).
The placental barrier is more permeable to CO2 (than O2), and its exchange is more or less complete diffuses across placenta into maternal blood
Placental exchange of nutrients
Glucose: transported by facilitated diffusion via GLUT1 carrier (from maternal to fetal side); fetal glucose usually in equilibrium with mother.
Amino acids: actively transported; specific transporters for all essential amino acids; concentration higher in plasma of fetus than that in mother.
Lipids: phospholipids are hydrolysed to free fatty acids (FFAs), which freely diffuse (passively) down their concentration gradient(s) to fetus.
Placental exchange of fetal waste products
Urea: produced by protein metabolism; passively diffuses into maternal blood (placenta) for excretion.
Bilirubin: formed by breakdown of Hb (i.e. red blood cells):
- As above; crosses placenta to undergo conjugation to bilirubin glucuronide in maternal liver (fetal liver is immature: has insufficient amounts of hepatic conjugation enzymes).
- Bilirubin glucuronide is water-soluble can be excreted.
- Build-up in fetal blood can cause brain damage (crosses BBB…)
-> Kernicterus: brain damage caused by bilirubin in newborns with severe jaundice motor function impairments
Role of placenta: endocrine organ
- hCG increases until it reahes max. conc. near end of first trimester then decreases to a low level ater
- Progesterone continues to increase until it levels off near the end of pregnancy. early in pregnancy progesterone is produced by corpus luteum in ovary by second trimester shifts to placenta
- Estrogen increases slowly throughout pregnancy but more rapidly at the end of pregnancy. early in pregnancy its produces by the ovary by second trimester, it shifts to placenta
hCG
Human chorionic gonadotropin (hCG)
hCG is secreted by trophoblast cells of the embryo:
- Luteotrophic role: maintains corpus luteum; luteal progesterone is required for first 6-8 weeks of pregnancy; hCG levels decline by 10th week (but still produced until end of pregnancy).
Other actions:
- Acts on maternal hypothalamus to inhibit FSH and LH synthesis.
- Promotes uterine quiescence (myometrial smooth muscle).
- Prevents immune rejection of the fetus (by the mother).
- Stimulates differentiation of the male reproductive tract.
progesterone & estrogen during pregnancy
Successful pregnancy requires adequate levels of progesterone:
- First 8 weeks produced by corpus luteum; after, progesterone of placental origin takes over.
Key actions of progesterone:
- Prevents menstruation.
- Keep uterine smooth muscle quiescent.
- Stimulates development of breast tissue.
- Suppresses ovulation.
- Prevents immunorejection of the fetus
Human placental lactogen (hPL) aka human chorionic somatomammotropin (hCS)
hPL: GH like effect in inducing resistance to insulin action in the mother .> limits maternal glucose utilisation
hPL is secreted by the placenta around the time when hCG levels are beginning to fall (week 8-10):
- Peptide hormone produced by syncytiotrophoblast: similar in structure to prolactin and growth hormone (GH).
- Mammotrophic action: stimulates proliferation of breast tissue in preparation for lactation
Other actions: : helps to adjust maternal plasma levels of, e.g., glucose (makes tissue less sensitive to insulin), amino acids (reduces gluconeogenesis), and FFAs (increases lipolysis):-> maintains favourable concentration gradients
change sin maternal physiology
At full term, the fetus occupies considerable space -> displacement and/or compression of various organs/ systems (by enlarging uterus)
changes in maternal physiology: cardiovascular system
Maternal cardiac output (CO) ↑ by 30-50% to satisfy demands of the uterus and placenta for nutrients/waste disposal:
- Heart rate (HR) and stroke volume (SV) increases.
Changes in plasma volume and maternal blood composition:
- Plasma/blood volume ↑ by ~40-50%; ~30% ↑ in RBC mass, although Hb content often falls (may need iron supplements).
- Increased levels of fibrinogen and specific clotting factors ↑ the risk of deep vein thrombosis.
Mid-pregnancy, maternal arterial blood pressure (BP) often falls (as peripheral resistance falls), but may increase slightly at full term:
- Significant increase in arterial BP with oedema, or presence of proteins in urine (proteinuria) indicative of pre-eclampsia risk.
changes in maternal physiology: Renal system
Both maternal renal function and body fluid balance reflect CV changes:
- Glomerular filtration rate (GFR) is ↑ by 30-50% (↑ in CO, ↑ in renal blood flow), and output of renin & aldosterone is stimulated:
Plasma levels of urea and creatinine ↓ (↑ urine production).
- Note: in late gestation, there may be a slight drop in GFR.
- Total body water ↑ by 6-8 liters; ↓ in plasma osmolality:
Contributes to weight gain..!
Results in oedema (a normal consequence of pregnancy, if to a small degree).
Increased thirst experienced may be due to ↑ levels of angiotensin II (recap RAAS).
Pre-eclampsia & eclampsia: serious disorders of pregnancy
Hypertensive disease in pregnancy is a major cause of perinatal mobidity and mortality
Pre-eclampsia occurs in ~3-10% of pregnancies; pathophysiology & cause(s) are not well understood:
- Common in final trimester.
- Classed as severe if arterial BP = 160/110 mmHg.
- Potentially caused by incomplete trophoblastic invasion of maternal spiral arteries which remain responsive to vasoconstrictors
No effect-> reduction in placental blood flow -> fetal growth retardation
Eclampsia: potentially fatal condition (0.05% of all deliveries); extreme hypertension (high BP):
- changes in intracranial pressure, seizures, coma.
- Mother: ↑ risk of cerebral haemorrhage, renal failure…
Nutritional requirements of pregnancy
Maternal nutrition is crucial for the fetus. Malnutrition early in pregnancy can cause specific abnormalities that are congenital (i.e. existing at birth).
cruicial for example: Folate
