Physiology of Pregnancy Flashcards
Length of trimester
12 weeks- measured from the first day of the menstrual cycle. Conception typically occurs in week 3 coinciding with ovulation.
What is decidualisation?
Changes to endometrium stromal cells of the uterus to prepare for embryo implantation. It involves change from fibroblast cells -> metabolically active decidual cells which forms the base of the placenta called the decidua. This is driven by progesterone.
What changes occur in decidualisation?
Endometrium of uterus undergoes changes to support the growth of the embryo in the early stages via histotrophic support
->Secretion of prolactin to provide uterine milk to the embryo
->Increase in vascularisation where arteries become more spiral and
->Cells become filled with glycogen and fat
Endometrial glands have the greatest secretion following blastocyst implantation once it hatches from the zona pellucida.
How does the embryo receive blood supply?
Intervillous space, located between the chorionic villi
What is the glycocalcyx in the embryo?
Epithelium progenitor which is important in cell-adhesion and signalling.
How does the synctiotrophoblast form?
Fusion of the cytotrophoblast. It is a single celled multineucleated unit which is highly invasive into the endometrium for remodelling of endometrial spiral arteries by altering their structure to enter spaces called lacunae in order to provide blood supply to the embryo.
Where it terminates in the lacunae is the foetal lobule that is the foundation of maternal nutrient supply.
What happens in the implantation stage?
Blastocyt hatches from the zona pellucida and glycocaclyx and causes alterations in the glycoprotein mucins of the endometrium, using fibronectin and integrin to bind to the uterus. Villi of the trophectoderm of the embryo interdigitate with villi epithelia for interaction with uterus. Portion of the trophoblast called the synctiotrophoblast fuses and invades into the endometrium for spiral artery remodelling.
What is required in initial implantation?
Blastocyt must use protease to alter mucin glycoproteins on the uterus which are anti-adhesive.
Which hormones are important in embryo implantation?
Oestrogen, leukemia inhibitory growth factor and epithelial growth factor.
What is the role of oestrogen?
Regulates implantation window and inhibits FSH and LH release.
Produced by the corpus luteum which improves vascularisation of the uterus. It stimulates the growth of the foetal adrenal gland. Responsible for foetal development of the organs and organ development.
What is the role of progesterone?
Progesterone causes systemic vasodilation of blood vessels and venous distensibility resulting in hypotension.
How is oestrogen synthesised in the foetus?
Foetal adrenal glands synthesise androgens which are converted to oestrogen via reductase enzyme.
What promotes attachment of the embryo to the uterus?
Leukemia inhibitory factor-cytokine which is induced by high levels of progesterone
What regulates the implantation window?
Oestrogen and progesterone.
When is the embryonic stage of pregnancy?
Week 3 to Week 8 of pregnancy- after fertilisation, the blastocyt becomes an embryo and begins to develop the body organs
When is the foetal stage of pregnancy?
Week 9 of pregnancy until birth
What happens in the first trimester in the embryo?
Fertilisation, implantation, initial development of bones, muscles and all body organs.
What happens in the first trimester in the mother?
Weight gain and nausea, nocturia
What happens in the 2nd trimester in the foetus?
Spine straightens, proportions of foetus changes, hair development, nervous system develops for Pain sensation.
What happens in the second trimester in the mother?
->Placental growth to accommodate growing foetus
-> Uterus rises to reduce bladder pressure
-> Hypervolemia occurs due to higher oestrogen and progesterone levels which increase RAAS system activity
What are the physical changes in trimester 2?
Uterus fundus rises to create bump
Fluid retention- Hypervolemia
Placenta overtakes endocrine role as corpus luteum regresses and cause drop in hCG
Foetus triples in size and eventually becomes larger than placenta
Quickening
What is quickening?
Sensation of movement of foetus in womb.
What happens in the third trimester in the foetus?
Growth in weight and development of body, brain, lungs and blood cells.
What happens in the third trimester in the mother?
Tiredness
Lactation of colostrum milk which is nutrient dense
Back pain
Restricted breathing: increased oxygen demands
Braxton-Hicks
Relaxin production
Why does shortness of breath occur in pregnancy?
Diaphragm rises which reduces lung capacity and increases lung resistance. High progesterone levels increase the sensitivity of the respiratory centre to carbon dioxide. Higher oestrogen levels increases the sensitivity of progesterone receptors in the brain.
What is Braxton-Hicks?
Contraction and relaxation of the womb during the second and third trimester typically in preparation of true labour.
How does oestrogen cause physiological changes in the mother?
Increases levels of nitric oxide for vasodilation, that results in increased blood volume. It also increases blood flow.
Increases hepatic angiotensin II for the RAAS system.
How does progesterone cause changes in pregnancy?
Causes vasodilation and increases aldosterone levels that leads to greater thirst and fluid retention. Combined with high oestrogen, it leads to swolle ankles/pitting oedema.
It relaxes the intestinal muscles and lower oesophageal sphincter which can cause constipation and gastric reflux. The gall bladder is also relaxed and increases risk of cholestasis due to reduced contraction.
What are the cardiac changes in pregnancy?
Heart function increases by 30-50% with Higher cardiac output, blood volume and faster heart rate and stroke volume due to oestrogen .There is an Increase in heart size and atrial size.
->Dilation of the blood vessels prevents hypertension due to effects of progesterone
Cardiac output will peak in 3rd trimester.
How much does heart size increase in pregnancy?
Heart increases in size by 12%.
What are the respiratory changes in pregnancy?
Lung function increases by 40% which causes 16-20% more oxygen to be consumed.
Diaphragm elevates to accommodate for foetus which reduces the functional residual capacity so the Rib cage is displaced upwards.
Thoracic breathing which means quicker, shallower breathing and higher tidal volume due to progesterone increasing the responsiveness to CO2, resulting in a mild state of respiratory alkalosis. The sensitivity of chemoreceptors is lowered
How do the kidneys change in pregnancy?
Kidneys produce more EPO which increase the levels of RBC and reticulocytes in order to compensate for increasing oxygen demands from the foetus.
Kidney size increases because of increased excretion.
Increased blood flow due to progesterone causing afferent arteriolar vasodilation which increases GFR and kidney size
How does the urinary system change in pregnancy?
Ureters are displaced which decreased bladder tone (contraction) This increases capacity for storage, leading to stasis and higher UTI risk
How does hameatocrit change in pregnancy?
Low Haematocrit/relative anaemia
Increase in RBC due to higher EPO production, however there is greater salt and water retention that causes increased plasma volume
More pro-coagulation factors are produced and platelet aggregation is more likely to occur, increasing the risk for hypercoagubility.
How does MCV change in pregnancy?
Mean size of RBC does not change
When does implantation occur in pregnancy?
Day 6
Source of progesterone production in non-pregnant women?
Granulosa cells within the Corpus luteum
Source of progesterone production in pregnant women?
First 10 weeks: corpus luteum
Following 10 weeks: Placenta
How does the embryo gain access to maternal blood supply in implantation?
Fragments of spiral arteries are engulf by the synctiotrophoblast which contain pores called lacunae which fill with maternal blood and act as precursors for intervillous lacunae.
How does the endometrial blood supply change in implantation?
There is a switch from histotrophic support to haematotrophic support. Synctiotrophoblasts expand and anastomose with spiral arteries and remodel to reduce looping and blood pressure of the arteries, before it enters pores called the lacunae to supply the embryo with low pressure, low resistance blood flow.
What is the synctium?
Barrier between the embryo and developing placenta formed by trophoblast cells. It provides protection from the foetus against infection from the mother.
What happens post-implantation?
Day 9/Week 3 Lacunae form in synctiotrophoblast which invade spiral arteries.
Cytotrophoblast forms pirmary, secondary, tertiary, stem and floating villi
Embryo receives nutrition from uterine gland secretion and destruction of uterine stroma during implantation via histotrophic support
What are the features of cytotrophoblast?
It anchors the foetus to maternal tissue and forms the chorionic villi. Maintains cellular individuality unlike the synctiotrophoblast which is a single unit structure.
What provides the embryo with support post-implantation?
Nutrition via:
Destruction of the stromal uterine cells
Histotroph gland secretion
What is histotrophic support?
Embryo receives additional nutrition from mother via uterine gland secretions such as uterine milk from prolactin and stores of glycogen and fat in the endometrium. This is the first source of nutrient support post-implantation
What is hCG?
LH analogue which binds to LH receptors on the corpus luteum for progesterone production. Produced by trophoblast cells and later placental. It maintains oestrogen and progesterone production of uterine lining thickening.
Why is hCG an important indicator in pregnancy?
Present in the blood 10-11 days after conception, peaking between 8-12 weeks. The levels of rapidly increasing hCG are important in tracking the pregnancy and foetus and is eliminated in the urine in the form of beta hCG.
What are the symptoms post-implantation?
After 7-9 days following implantation, there is a change in the body to pregnant physiology. There is suppression of menses, tender breasts, nausea and vomiting. Urinary frequency and constipation can occur.
What is the precursor to the placenta?
Trophoblast
What separates the epiblast and hypoblast in development?
Pluriblast
What happens to the hypoblast in development?
Hypoblast spreads down the trophoblast to become outer chorion membrane and outpouch called yolk sac
What surrounds the embryo?
Inner layer of the amnion
Outer layer of the chorion
What is the amnion?
Thin innermost membrane surrounding the embryo filled with fluid. It is formed from the ectoderm and mesoderm.
Which germ layers form the amnion?
Ectoderm and mesoderm
What is the chorion?
Outermost membrane surrounding the embryo consisting of the cytotrophoblast and the extra embryonic mesoderm.
Which germ layer forms the chorion?
It is formed from the trophoblast and mesoderm.
What provides nutrition and gas exchange to embryo prior to placenta formation?
Yolk sac- extraembryonic outpouch which later regresses. Formed of endoderm and mesoderm
When does histotrophic support end?
Week 12 where the Growth of embryo means there are greater exchange requirements so requires hameatrotrophic support via the placenta.
What is haematotrophic support?
Haematotrophic support is the transport of nutrients from the mother’s blood to the embryo via the placenta
What is the function of the chorionic villi?
Finger like projections to provide maximal contact with maternal blood for nutrient and gas exchange. It forms vessels to minimise the impact of reactive oxygen species due to hypoxia prior to placenta development.
What is the lacunae?
Pores in the synctiotrophoblast which allow the accumulation of nutrients to support growth.
What happens to maternal arteries at the beginning of pregnancy?
Synctiotrophoblast invasion of the spiral arteries causes remodelling into highly dilated open vessels via reducing looping. This reduces resistance to blood flow for embryo perfusion.
What is the blood pressure of the maternal blood supply?
Low blood pressure as spiral arteries are released into the lacunae of the synctiotrophoblast.
When do the villi develop?
Begin to develop the 4th week by sprouting from the chorion as primary villi and become fully vascularised between 5th and 6th weeks to become tertiary villi
What are the branches of the tertiary villi?
Floating villi and stem villi
What are the floating villi?
Villi floating freely in the intervillous space which take up nutrients from maternal blood pooled in the lacunae via diffusion into the embryo.
What is the stem villi?
Branch attached to the decidua maternal tissues and connects the tertiary villi to the outer layer.
How does the chorion become vascularised?
Secondary villi of the chorion expand into the synctiotrophoblast and contain a core of mesoderm which can form new blood vessels.
What is the origin of the chorionic villi?
Originates from the cytotrophoblast.
What is the structure of the chorionic villi?
Branching and vascularisation of villi to form tertiary villi become foetal blood vessels
What are the phases of the villi?
Primary villi: Villi arising directly from the cytotrophoblast in 3rd week
Secondary villi: Contains a core of extraembryonic mesoderm due to invasion of mesoderm growing through trophoblast
Tertiary villi: Blood vessels penetrating villi causes vascularisation. This penetrates the decidua of the uterus and form a layer.
How does the chorionic villi develop?
Primary-> Secondary-> Tertiary villi.
The tertiary villi lie on the synctiotrophoblast and grow towards the maternal decidua and creates a layer which becomes the future foetal side of the placenta called the chorionic plate. Cytotrophoblast regresses in the 2nd trimester, leaving behind the synctiotrophoblast
What is hemichorial placenta?
Limited cellular barrier between the mother and the foetus to not mix blood.
How is maternal and foetal blood supply separated?
Maternal blood sits in lacunae and bathe the villi of the synctiotrophoblast to prevent physical exchange of blood.
What is the placenta?
Organ which is foetal-derived and forms a physical connection between the mother and the foetus.
What does the placenta contain?
Contains maternal endometrial/spiral arteries which feed into the intervillous space. The intervillous space contains pools of maternal blood. Drains back into maternal circulation via uterine vein.
2 umbilical arteries: carries deoxygenated blood from body to organ placenta
1 umbilical vein: collects oxygenated blood from placenta organ to the foetus body
Where do the maternal and foetal supply join?
Umbilical cord which contains 2 umbilical arteries and 1 umbilical vein- there is an oxygen gradient which is higher in the mother
What separates maternal and foetal blood supply in the placenta?
Placental membraneseparates chorion and decidua.
What is the CO2 gradient between the maternal and foetal supply?
CO2 is higher in the foetal blood 2-3x more than maternal
What are the features of foetal haemoglobin?
Nucleated erythrocytes with a higher affinity for O2 than adult Hb
What is the main energy source for the foetus?
Glucose, which is transported across the placenta via GLUT receptors on the synctial membrane for glucose transfer which is oxidised form.
Which placental carriers are involved in glucose transport?
-> GLUT 1 which is found on microvilli and synctial membranes.
->GLUT 3, GLUT 4 and GLUT 12
What is the respiration pathway in the foetus metabolism occur in the foetus?
Foetus cannot perform gluconeogenesis due to low oxygen conditions so placenta promotes glycolysis.
How does placenta gain alternative energy sources to glucose?
Contains placental lipoprotein lipase which breaks down VLDL and chylomicrons. This creates fat stores in the placenta to synthesise hormones and inflammatory mediators to support pregnancy.
What are the placental fat stores?
Free fatty acids
Cholesterol
Glycerol
-> These are attained from lipoprotein lipase action on VLDL and chylomicrons into fat components.
Which hormones does the placenta synthesise?
hCG
Oestrogen
Progesterone
Somatomammotrophin
Which hormone is an indicator for placental function?
Progesterone which is responsible for the decidualisation reaction. It increases the uterine secretions.
During labour, it reduces uterine contractions.
What is the role of placental hCG?
Placental hCG begins to be produced at week 8-12 of pregnancy. It is closely related to TSH and binds to receptors for T3 and T4 production.
What is the role of placental oestrogen?
Induces proliferation of the myometrium
Relaxes the pelvic ligaments and increases elasticity of pubic symphysis in preparation for childbirth.
It peaks at week 40.
When does oestrogen reach its peak in pregnancy?
Week 40
How does the foetus synthesise oestrogen?
1)Uptake of maternal androgens
OR
2) Foetal androgen 16-alpha-hydroxylated steroid from adrenal glands
-> oestrogen via reductase enzyme.
What is the role of placental progesterone?
Increases uterine secretions
Induces decidualisation
Inhibits uterine contractions
Causes systemic relaxation of the muscles, blood vessels and airways in the maternal body,
What hormone increases uterine contractions?
Oxytocin- it inhibits uterine contraction and stimulates contraction
What hormone decreases uterine contractions?
Progesterone- it induces uterine relaxation and inhibits contraction
How does oestrogen affect blood volume?
Increases angiogenesis,
Venous distensibility (when BP increases, dilation occurs)
Increased blood flow
How does progesterone affect blood volume?
Increases vasodilation. Increases aldosterone and effect of thirst centre which promotes oedema.
What is pre-eclampsia?
High blood pressure which occurs after 20 weeks gestation during pregnancy which can lead to kidney damage and proteinuria.
What is the average weight gain in pregnancy?
11kg which is mainly from the uterus and placenta. Partly due to higher fluids in body, breast increase and fat stores.
What are the increased caloric intakes?
No extra caloric intake in 1st trimester.
Second: 200-300
Third: 400+
How does female fertility change?
Reduced ovarian function, reserve and uterine function which reduces chances of conception
What causes the oxygen disassociation curve to shift to the left?
Higher Hb affinity for O2 due to lower pCO2, H, 2,3BPG and temperature
What causes the oxygen disassociation curve to shift to the right?
Lower Hb affinity for O2 due to
increase in CO2, H+, 2,3BPG and temperature
How does foetal Hb affect the oxygen disassociation curve?
Shifts the curve to the left which increases O2 saturation
What is eclampsia?
High blood pressure which results in seizures.
What is a consequence of excessive uterus size in pregnancy?
Impaired function of the inferior vena cava. This reduces preload and results in varicose veins.
