Reproductive System Week 8 Flashcards
What does an antenatal screening involve?
History and examination - identify risk factors - e.g. Gestational diabetes
Blood test - blood group (Rh neg - HDN), Haemoglobin (iron store- foetal demands), Infection (teratogenic- syphilis, HIV)
Urinalysis - protein (preeclampsia - hypertension –> proteinuria)
Why do physiological adaptation occur in the mother in response to demands created by the pregnancy?
Support the foetus (volume, nutritional and oxygen support, clearance of foetal waste)
Protection of foetus (from starvation, drugs, toxins)
Preparation of uterus for labour
Protection of the mother from potential cardiovascular injury at delivery
What factors affect the ability of the mother to adapt to pregnancy?
Maternal age, ethnicity and genetic factors
Which organ systems are required to adapt to the demands of pregnancy?
All
Quality, degree and timing of the adaptation varies from one individual to another and from one organ system to another
Describe the adaptations of the maternal cardiovascular system in response to pregnancy
Progesterone decreases systemic vascular resistance (25-30%) early in pregnancy (T1) –> decreased blood pressure –> cardiac output increases from T1 by 30-50% (HR (15%) and SV (35%) both increase)
Activation of the renin-angiotensin system –> increased circulating angiotensin II –> encourages sodium and water retention (40% increase in blood volume) and directly constricts the peripheral vasculature
Blood pressure reaches lowest point at week 20-24 and returns to normal around term (T3)
There is a 20% increase in BP during labour with a rapid resolution post-partum
The initial hypotension of pregnancy increases the risk of vasovagal episodes and nausea and can mask existing hypertension (risk factor for preeclampsia)
The hypotension of the third trimester is contributed to by the aortocaval compression by the gravid uterus - reduces return to the heart - therefore dont leave pregnant women supine for extended periods of time –> reduces blood to placenta + oxygen to foetus
Endothelium controls vascular permeability and contributes to control of vascular tone –> vasodilation of pregnancy
State the differences between a normal and pre-eclamptic pregnancy
Normal pregnancy - vasodilation, plasma expanded
Pre-eclampsia - precursor to fits in pregnancy - vasoconstriction, plasma contracted - increase in BP to compensate for vasoconstricted state (hypertension)- defect in placentation, poor uteroplacental circulation, widespread endothelial dysfunction
Describe the adaptations to the urinary system in pregnant women
GFR increase by 55% early in pregnancy –> renal plasma flow increases (60-80%) and functional renal reserve decreases
GFR increase –> increase in creatinine clearance (40-50%) and a 25% decrease in serum creatinine and urea concentrations
Increased GFR –> increased filtered sodium –> aldosterone levels increase 2-3x to reabsorb this
Increased GFR –> decreased reabsorption of glucose –> 15% of normal pregnant women exhibit glycosuria
Mild hydronephrosis and hydroureter are common sonography findings due to high progesterone levels and partial obstruction from the gravid uterus
5% of pregnant women have bacteria in their urine - pregnancy does not increase incidence of asymptomatic bacteriuria but such women are 20-30% more likely to develop pyelonephritis
Pyelonephritis can lead to pre-term labour
What are the normal ranges for serum urea and creatinine in pregnant women?
Creatinine - 35-62 micromol/l in first trimester, 35-71 micromol/l in second trimester and 35-80 micromol/l in third trimester
Urea - 2.5-4.3 mmol/l in first trimester, 1.1-4.6 mmol/l in second trimester, 1.1-3.9 mmol/l in third trimester
Describe the adaptations made to the respiratory system in pregnant women
Designed to optimise maternal and foetal oxygenation, and facilitate transfer of CO2 waste from foetus to mother
Many pregnant women complain of a subjective perception of shortness of breath (dyspnea) in the absence of pathology - reason unclear
Mechanics change - ribs flare outward (AP and transverse diameters increase) and the level of the diaphragm rises 4cm
Tidal volume increases by 200ml (40%) –> functional residual capacity decreases (T3) and a 200ml (20%) decrease in residual volume –> less air in lungs at end of expiration
Vital capacity stays the same, total lung capacity is approximately the same (slight decrease)
Physiological hyperventilation - increased CO2 production from foetus, increased respiratory drive effect from progesterone
respiratory rate does not change
Physiological dyspnea due to progesterone-driven hyperventilation
Net result is increase in minute ventilation and a drop in arterial PCO2 - arterial PO2 is essentially unchanged (slight increase)
O2 consumption increases by 20%
Compensatory decrease in bicarbonate enables the pH to remain unchanged - buffering capacity reduced - increased risk of metabolic acidosis
A state of compensated respiratory alkalosis
FEV1 is unchanged
Describe the changes in carbohydrate metabolism during pregnancy
Increase in maternal peripheral insulin resistance - placental hormones have anti-insulin activity
Switch to gluconeogenesis and alternative fuels
Produced by human placental lactogen and prolactin, oestrogen/progesterone and cortisol
Decrease in fasting blood glucose
Increase in post-prandial blood glucose
What are the risk factors for gestational diabetes and what are the clinical consequences?
>25 years old BMI > 25kg/m2 First-degree relative with diabetes History of GDM Insulin resistance/PCOS Prior macrosomic infant Prior unexplained late foetal demise Persistent glycosuria Member of ethnic or racial group with high prevalence of diabetes (Hispanic, Native American, asian, African american
Oral glucose tolerance test required
Little risk to the mother - not at risk of DKA because can produce insulin (just resistant)
- associated with increase in infant and mother birth trauma, Caesarian delivery, operative vaginal delivery and perinatal morbidity and mortality - directly related to its size
Examples of birth injuries to foetus - orthopaedic, neurological - brachial plexus (Erb’s palsy)
Macrosomia - estimated foetal weight >4500g
Still birth
Increased rate of congenital defects
Goal of treatment is to prevent macrosomia and its resultant complications by maintaining maternal blood glucose at desirable levels - diet change, moderate exercise, daily glucose monitoring weekly antepartum visits to monitor glucose - if initial fasting levels are too high or dieting doesnt work start hypoglycaemic treatment - insulin
After delivery no further treatment is required - the source of the anti-insulin hormones has been removed
What is gestational diabetes?
Any form of glucose intolerance with the onset of pregnancy or first recognised during pregnancy
Complicates approximately 5% of all pregnancies
Likely includes some women who have undiagnosed pregestational diabetes
What is preeclampsia?
Defined as new-onset significant hypertension and proteinuria after 20 weeks’ gestation
Non-dependant oedema (swelling of hands and face) no longer a prerequisite for diagnosis
Primary defect - complete or partial failure of second wave of trophoblast invasion responsible for remodelling of maternal spiral arterioles and establishment of the definitive uteroplacental circulation
This process if typically complete by 16-18 weeks gestation
If deficient - spiral arterioles unable to dilate adequately to meet demands of growing foetoplacental unit - leads to placental ischaemia wth the release of a toxaemic factor that damages the vasculature throughout the maternal circulation - resulting in wide-spread vasospasm and endothelial injury
Clinical manifestations only appear in the latter half of pregnancy
What are the risk factors for pre-eclampsia?
Cant accurately predict whether an individual will develop preeclampsia or prevent it
Nulliparity African-American Extremes of age Multiple gestation Family history Prior history Chronic hypertension Chronic renal disease Obesity Diabetes
What is the treatment for preeclampsia?
Delivery is the only effective treatment
Should be considered in all women with mild preeclampsia once a favourable gestational age is reached (36-37 weeks)
Delivery is recommended for all women with severe preeclampsia regardless of gestational age unless proteinuria alone (doesnt correlate with maternal or perinatal outcome), foetal intrauterine growth restriction alone remote from term (Should be kept in hospital with foetal testing daily), BP criteria alone <32 weeks gestation (careful BP control)
Routine use of antihypertensive medications do not change the course of preeclampsia for either the mother or the foetus - can prevent stroke during delivery
Given magnesium sulphate seizure prophylaxis during labour and for 24-48 hours postpartum
If circumstances permit - antenatal corticosteroids should be administered and delivery delayed for 24-48 hours for a protective effect on foetus
No proven benefit to Caesarian - if no response to cervical ripening after 12 hours - should be considered
Usually resolves within few days of delivery - diuresis accurate indicator of resolution
Describe the changes in lipid metabolism in the pregnant woman
Increase in lipolysis from T2
Increase in plasma free fatty acids on fasting - dont cross the placenta unless essential fatty acids
Provide substrate for maternal metabolism - leaves glucose for foetus
Why is pregnancy associated with an increased risk of ketoacidosis?
Lack of bicarbonate because respiratory alkalosis compensated by metabolic acidosis
Describe the adaptations made to the endocrine system in the pregnant woman
Oestrogen increases hepatic production of thyroid-binding globulin –> increase in total thyroid hormone concentration
TSH, free T3 and free T4 remain unchanged
T3 and T4 increase overall
HCG can cause TSH to be low in normal pregnancies
Describe the adaptations made to the gastrointestinal system during pregnancy
Alterations in the position of the viscera - appendix moves to RUQ as uterus enlarges - localisation of pain during appendicitis
Nausea occurs in >70% of pregnancies - normally resolves by 17 weeks
Progesterone causes relaxation of GI smooth muscle –> delayed gastric emptying and increased reflux, predisposed to cholelithiasis (gallstone) - majority cholesterol stones (also due to chemical changes)
Increased risk of pancreatitis - due to increased stone risk or consequence of hyperlipidaemia
Diabetogenic state - ensures continuous supply of glucose to foetus
Describe the adaptations made to the haematological system during pregnancy
Increased intravascular volume (40-50%)- results in dilutional anaemia (physiological) Elevated erythropoietin levels lead to compensatory increase in total red cell mass (20-30%) but doesnt fully correct anaemia Iron deficiency anaemia and folate deficiency can occur due to high demands Haemoglobinopathies (rare) Modest increase in white cell count (leukocytosis) - differential count should not change Mild thrombocytopenia (low platelet) is seen in 10% of pregnancies - dilutional and rarely clinically significant Hypercoaguable state - increased circulating levels of factor II (fibrinogen), VII, IX and X - fibrin deposition at implantation site - reduced fibrinolysis- protect the mother from excessive blood loss at delivery but predispose to thromboembolism - added to this venodilation and stasis Warfarin crosses the placenta and is teratogenic
Describe the adaptations made to the immune system during pregnancy
Foetus is an allograft - genetically distinct
Non-specific suppression of local immune response at the maternal-foetal interface – >viral infection in particular is more common in pregnancy (as well as TB)
Transfer of antibodies :
- Haemolytic disease - Rh - mother with previous Rh + pregnancy produces IgG class antibodies - can cross the placenta in next pregnancy - prophylaxis needed
- Graves’ disease and Hashimoto’s thyroiditis - can cross the placenta
In very early embryonic development, establishment of which structure takes precedence?
The placenta
Describe implantation
Interstitial - uterine epithelium is breached and the conceptus implants within the stroma - small bleed can occur - can be confused with light menstrual period
Placental membrane becomes progressively thinner as the needs of the foetus increase
By 3rd trimester placenta is haemomonochorial -one layer of trophoblast separate the maternal blood from the foetal capillary wall
What are the aims of implantation?
Establish the basic unit of exchange:
- primary villi - early finger-like projections of trophoblast
- secondary villi - invasion of mesenchyme into core
- tertiary villi - invasion of mesenchyme core by foetal vessels
Anchor the placenta - establishment of the outermost cytotrophoblast shell (not same as the layer under the syncytiotrophoblast)
Establish maternal blood flow within the placenta
Describe some implantation defects
Ectopic pregnancy:
- implantation at a site other than the uterine body (most commonly Fallopian tube)
- can be peritoneal or ovarian
- can very quickly become life-threatening emergency
Placenta praevia:
- implantation in the lower uterine segment - placenta grows across exit - birth canal cant function
- can cause haemorrhage in pregnancy
- requires c-section delivery
Invasion incomplete:
- placental insufficiency - poor growth and development of foetus
- pre-eclampsia - poor growth and development of foetus, maternal syndrome
How is the endometrium prepared for implantation?
Predecidual cells - specialised cells in the endometrium, control implantation - surround the spiral arterioles - maintain the amount of implantation at optimum levels (not too much or too little)
Elaboration of spiral arterial blood supply
Describe decidualisaion
Decidual reaction provides the balancing force for the invasive force of the trophoblast
The decidual cells are only present in endometrium - ectopic pregnancy consequences–> invasive, uncontrolled process –> rupture of vessels
Conditions characterised by excessive invasion if this process if dysfunctional - placenta accreta, increta and percreta
Describe the remodelling of the spiral arteries
Creation of low resistance vascular bed
Maintains high flow required to meet foetal demand - particularly late gestation
Trophoblast starts to invade maternal vessels - come to be lined by this trophoblastic foetal tissue - allows them to be low resistance and high flow
Pre-eclampsia - inadequate modification of the spiral artery walls
Give a summary of the development of the foetal membranes
Early embryonic development - villi form all over the chorion (week 5)
The decidua capsularis is around the outer edge of the chorion and the decidua parietalis is the opposite endometrial wall
Week 12 - final disc shape achieved - chorion loses vili and becomes smooth (chorion laeve ) apart from where it is in contact with the decidua basalis (the endometrium underneath the implanted conceptus)
Week 22 - amnion and chorion fuse to become a composite membrane - fuse with decidua parietalis
How are membranes shared in twins?
The degree to which membranes are shared in monozygotic twins varies
Can have completely separate chorion and amniotic sacs, same chorion with different amniotic sacs or the same chorion and amniotic sac
Monochorionic twins are at risk of twin to twin transfusion syndrome - circulations get crossed and blood and nutrients get taken from one baby and into the other - dangerous for both babies
Draw a diagram showing the layers of the placental membrane including the primary, secondary and tertiary villi, as well as the anchoring villi, the syncytiotrophoblast, cytiotrophoblast and decidua basalis
Look at picture
What happens to the placenta between the 1st trimester and term?
Placental barrier becomes thinner - cytotrophoblast layer disappears under the syncytiotrophoblast (apart from occassional cell) –> capillaries pushed to the margin of the villi
Surface area for exchange dramatically increased - villi no.
Describe the vessels inside the umbilical cord
Two umbilical ARTERIES - deoxygenated blood AWAY from the foetal heart and to the placenta
One umbilical VEIN - oxygenated blood from the placenta TOWARDS the foetal heart
What metabolic role does the placenta play?
Synthesis of glycogen, cholesterol (huge capacity !! - steroid hormones synthesised from this) and fatty acids
Which hormones are produced by the placenta?
Steroid hormones - progesterone and oestrogen - responsible for maintaining pregnancy - takes over from corpus luteum 11th week –> hCG comes down
Protein hormones: - human chorionic gonadotropin :
- produced during 1st 2 months of pregnancy
- supports secretory function of corpus luteum until capable of own oestrogen and progesterone synthesis and secretion
- produced by syncytiotrophoblast - pregnancy specific - secreted in maternal urine - basis for pregnancy testing
- trophoblast disease : * molar pregnancy (hydatidiform mole) - abnormal placental growth - no embryo - massive over production of hCG
- choriocarcinoma (malignant) - monitor HCG for treatment efficacy
- twin pregnancy - can give large hCG
Human chorionic thyrotrophin
Human chorionic somatomammotrophin
Human chorionic corticotrophin
How do placental hormones influence maternal metabolism?
Progesterone - increased appetite –> fat stores
HCS/hPL - increase glucose availability to foetus
Describe mechanisms of transport across the placenta
Simple diffusion - high to low concentration (gradient):
- water, urea+uric acid, electrolytes, gases
- gas transport is flow-limited (depends on good flow through the circulation) not diffusion-limited - foetal O2 stores are small - maintenance of adequate flow essential - relies on correct implantation and good management of labour
Facilitated diffusion - glucose transport
Active transport - specific “transporters” expressed by the syncytiotrophoblast:
- amino acids, iron, vitamins
- IgG
How does the foetus acquire passive immunity?
Foetal immune system is immature even after birth
Passive immunity is a receptor-mediated process, maturing as pregnancy develops
Only IgG can cross the placenta - breast milk contains Ig of different class
Active transport - IgG concentrations in foetal blood exceed those in maternal blood - requires energy - against concentration gradient
Describe how transport across the placenta can lead to unintentional outcomes (e.g. The wrong things are going across)
Placenta isnt a true barrier
Teratogens access the foetus via the placenta
Unintentional outcomes from physiological process
What is a teratogen? Give some examples
A substance that causes congenital abnormalities/birth defects or death of the foetus via a toxic effect
Thalidomide
Alcohol
Therapeutic drugs
Mercury
Drugs of abuse
Cigarette smoke (not technically teratogen but causes low birth weight)
What is haemolytic disease of the newborn?
Rhesus blood group incompatibility of the mother and foetus
Mother is Rh negative - previous birth of RhD positive child sensitised her to the Rh antigen or a blood transfusion with RhD positive blood
Can cross the placenta and attack foetal cells in next pregnancy
Uncommon now due to prophylactic treatment - anti-RhD Ig postnatally (or within 72 hours of a sensitising event) and antenatally in the third trimester in all RhD negative women
Which infectious agents are dangerous to the foetus?
Varicella zoster Cytomegalovirus Treponema pallidum Toxoplasma Gondi Rubella - immunisation available- causes microcephaly, PDA and cataracts Zika HIV
What would you expect to happen to the placenta if the mother is a smoker or living at high altitudes?
The interhaemal distance becomes even thinner than usual to compensate in situations where the demand for transported materials or the restriction on the maternal side leads to a deficit
This compensation has a limit - can be exceeded –> placental defects among the major risk factors for growth restriction –> linked to long term adult health problems (barker hypothesis)
What is the Barker hypothesis?
The phenomenon where impaired foetal growth leads to long term adult health problems
What happens if the placenta fragments during labour?
Can result in retained placenta - impairs shutdown of utero-placental circulation and can lead to serious post-partum haemorrhage
What kind of blood supply are the utero-placental and foetal-placental circulations?
Counter-current
What tissues constitute the placental barrier in the first trimester?
Foetal capillary endothelium, mesenchyme connective tissue, cytotrophoblast, syncytiotrophoblast
What tissues constitute the placental barrier in the third trimester?
Foetal capillary endothelium, syncytiotrophoblast
When do hCG levels begin to decline and why?
Week 11
Because the placenta is capable of taking over the role of oestrogen and progesterone synthesis and secretion
Corpus Luteum not needed anymore
How does alcohol cross the placenta?
Simple diffusion
Lipid soluble
Can lead to FAS/ARND
Why is cytomegalovirus a significant hazard during pregnancy?
Can cross the placenta
Is a teratogen - damage to the embryo and foetus
What tissue of maternal origin is shed with the afterbirth during labour?
The decidua
At what gestational age does placental IgG plasma concentration exceed maternal IgG plasma concentration?
Around 35 weeks
Could a neonatal immune disease be mediated by IgM?
No - only IgG can cross the placenta
What role does hCG perform?
Stimulates the corpus luteum to produce oestrogen and progesterone to maintain the pregnancy
Depresses humoral immunity - probably necessary to prevent rejection of the placenta by the mother and vice versa
What consequence does the depression of humoral immunity have on the mother?
More susceptible to viral infections and TB in particular
Which oestrogen best indicates foetal progression and why?
Oestriol - dependant on foetal adrenal and liver metabolism, as well as placental function - low levels indicate foetal distress –>early delivery may be desirable
Which hormones stimulate breast growth in the mother?
Oestrogen
Progesterone
Prolactin
Where is inhibin secreted from and how does it prevent further pregnancies?
Corpus luteum and placenta
Inhibits FSH - blocking follicular growth
What processes enable the mother to preserve fat for later in pregnancy?
Progesterone stimulates appetite and promotes fat storage
Maternal preparation - breast growth - may also contribute
What is the other name for human placental lactogen?
Human chorionic somatomammotropin
What job does hPL/hCS perform?
Increases maternal peripheral insulin resistance
Increases maternal lipolysis of the fat stores built up in early pregnancy - since the mother can become hypoglycaemic between meals
What happens to mean BP during pregnancy due to the increased plasma volume and CO?
Stays the same
Systolic BP increases slightly (increased SV) and diastolic BP decreases slightly (flow into additional tissues)
What changes in the heart may be apparent on examination of a pregnant woman?
Upward displacement, hypertrophy, flow murmurs are common
What effect do the increasing progesterone levels have on the peripheral circulation and what can the clinical consequences be?
Increased peripheral vasodilation
May be experiences as ‘feeling the heat’, easy to sweat, nasal congestion
Can cause hypotension
Venous distension and engorgement - varicose veins and haemorrhoids
What factors contribute to the venous distension experienced in late pregnancy and what are the consequences?
Smooth muscle relaxation by progesterone
Mechanical pressure of uterus on IVC when recumbent
Increased blood volume
Haemorrhoids
Varicose veins
What effect does the increased renal blood flow have on GFR?
Increase by 160%
How does the body compensate for the increase in GFR during pregnancy?
Secretion of renin, aldosterone and angiotensin II- conserve sodium
What effects can the uterus resting on the ureters have ?
Increased intraureteral tone, urethral dilatation, hydro-ureter, hydronephrosis
Also caused by smooth muscle relaxing effects of progesterone
Why is pregnancy associated with an increase in urinary incontinence?
Pressure on the bladder from enlarged uterus - engagement of foetal head towards end of pregnancy
Describe the changes in calcium metabolism during pregnancy
Placenta contributes to synthesis of calcitriol
Increases uptake of calcium from maternal gut
Facilitates skeletal formation and growth of foetus
Expectant mother encouraged to increase their intake of calcium by 70%
PTH rises in 3rd trimester - enhancing calcium mobilisation from maternal bone - increasing availability to the foetus
Describe how CO, HR, O2 consumption and tidal volume change during pregnancy
CO increase by 40%
HR increase to 80-90 bpm
O2 consumption increase by 15%
Tidal volume increase by 40%
How does the sustained hyperglycaemia of gestational diabetes affect foetal glucose levels and what are the consequences of this?
Causes foetal hyperglycaemia
Foetus increases insulin secretion (not exposed to same levels of hPL as mother)
Stored as fat (macrosomia)
Enlarged foetal liver (glycogen storage)
Difficult delivery - large baby
Trauma such as Erbs palsy
Caesarian may be required
Once isolated from maternal supply of glucose neonate may experience a reflex hypoglycaemia due to high circulating levels of insulin - brain particularly at risk of damage from hypoglycaemia - does not have glycogen storage
Other: Prematurity Impaired lung maturation Respiratory disorders of the newborn Cardiac, neural tube formation and other congenital malformations may occur if conception occurs in period of hyperglycaemia Polcythemia (haematocrit >55%)
Describe how a physiological anaemia occurs during pregnancy
The plasma volume expands in the second trimester to meet the nutritional requirement of the foetal-placental unit
Erythropoietin stimulated increase in blood cell mass –> increase in Hb levels doesnt happen until later
Therefore there is a dilutional or physiological anaemia - Hb appears to fall
Why does the mother need more iron during pregnancy?
For the Hb in her expanded blood volume
How else is iron turnover changed during pregnancy?
No menstruation
What symptoms may the mother experience due to this physiological anaemia?
Asymptomatic or easily fatiguable, breathless
How is iron deficiency anaemia treated during pregnancy?
Oral iron sulphate or gluconate
What are the consequences of anaemia to the foetal-placental unit during pregnancy?
Poor perfusion of foetal-placental unit
Foetal growth retardation
Anaemic women have 3-5 times higher mortality rate in pregnancy
Still birth rate is up to 6 times higher
How does smoking affect the O2 flow to the foetus?
Carbon monoxide in maternal blood - shifts the Hb-O2 curve to the left - so the Hb is in a tighter state - less O2 is released to the foetus for the same pO2 - may not get any
Why are steroid given to babies where delivery is necessary e.g. In pre-eclampsia?
To stimulate and speed up the development of tissues such as the lungs which develop later
What signs and symptoms suggest that a mild preeclampsia is worsening?
Increasing diastolic BP Persistent and worsening albuminuria Oliguria (low urine output) Thrombocytopenia Elevated liver enzymes Lack of foetal growth Oligohydraminos (deficiency of amniotic fluid) Pulmonary oedema Headache Visual complaints
Eclampsia - onset of fits in pregnancy
How would you treat a pregnant women who did have an eclamptic fit?
Maintain airway, administer oxygen, place on left side (enhance uterine perfusion) and maintain her safety during the convulsion
Magnesium is given by IV bolus - then continuous infusion to relieve vasospasm and stop the fitting
Diazepam or thiopentone may be needed for recurring fits
Hydralazine required for blood pressure control
Once stable assess foetus - maintain optimum fluid/oxygen/positioning
Delivery is the definitive treatment for eclampsia - Caesarian normally required unless cervix extremely favourable
What complications are associated with multiple pregnancies?
Increased incidence of pregnancy induced hypertension anaemia polyhydramnios preterm labour perinatal mortality antepartum haemorrhage.
