Name 4 maternal symptoms in early pregnancy
Nausea Constipation Lethargy Breast tenderness
Name 4 unwanted effects of progesterone during pregnancy?
Constipation Reflux Oedema Progesterone + mechanical: Haemorrhoids Flushes
What is the basis of pregnancy testing?
Based on the detection of hCG hCG is synthesised by the syncytiotrophoblast within 6-7 days of fertilisation.
It binds to luteotrophic receptors in the ovary and ensures the corpus luteum is maintained so there is continued production of progesterone required to support pregnancy until the placenta has developed.
N.B. biochemical pregnancy does not equal clinical pregnancy. 50% of biochemical pregnancies do not result in clinical pregnancy
Describe the cardiovascular changes that occur in pregnancy
Increase in cardiac output and haemodynamic changes.
Vasodilation stimulated by the uteroplacental vascular bed reduces TPR. This is compensated for by a rise in cardiac output (by raising stroke volume)
- Reduced TPR triggers actiavtion of RAAS.maternal plasma volume increases ~40% by 32 weeks gestation
Describe how cardiovascular changes during pregnancy are acheived
Rapidly growing uteroplacental vascular bed acts as an arteriovenous anastomosis
Fall in TPR is mediated by:
- inhibition of vascular smooth muscle tone by progesterone
- oestriol activates NOS in endothelial cells, increases NO (vasodilation)
- vasodilatory prostaglandins and prostacyclin released by placental endothelial cells (potent vasodilators)
Fall in TPR causes an increase in CO by increasing SV.
SV increased by an early increase in ventricular muscle and end diastolic volume. The heart is also physiologically dilated with increased contractility.
Reduced TPR lowers renal bp, stimulating the release of renin. This actiavtes the RAAS to increase sodium and water reabsorption and therefore increased plasma volume.
Why will a bp measurement taken from a pregnant woman in the supine position be innacurate?
In the supine position there is compression of the aorta and vena cava by the uterus. This reduces venous return, and therefore reduces cardiac output (up to 25-33%)
How can pregnancy result in varicose veins?
Pressure of the gravid uterus on the vena cava can restrict venous drainage from the legs, damaging the valves in the veins.
Describe the cardiovascular changes that occur in labour
Increase in cardiac output
Contractions lead to an autotransfusion of blood back into the circulation (300-500ml)
Sympathetic response to pain and anxiety increase heart rate and blood pressure
Cardiac output is increased during and between contractions
Describe the cardiovascular changes that occur after delivery
There is an immediate rise in blood pressure due to contraction of the uterus and relieved compression of the IVC
Cadriac output increases (60-80%)
Within an hour, cardiac output falls back to non-pregnant levels
What are the symptoms of the haemodynamic changes in pregnancy?
Palpitations: Cardiac output increases due to the fall in TPR by increasing SV. Maternal heart rate also increases to 80-90bpm.
Feeling hot: Rise in cardiac output increases blood flow to the uterus, breasts and skin. Increase in skin blood flow allows more heat loss in the face
Fainting: BP falls during pregnancy, but rises towards term. Compression of the VC reduces venous return.
Describe the changes in blood pressure that occur in pregnancy
In early pregnancy: There is a reduced diastolic pressure, but the systolic blood pressure does not change. This results in a wider pulse pressure.
BP falls from the end of the 1st trimester due to a fall in TPR
In late pregnancy: BP rises,
What are the common cardiovascular complications of pregnancy?
Haemodynamic changes of pregnancy increase risk of complications in women with pre-existing cardiac disease
Women with cardiac compromise are most at risk of pulmonary oedema during the second stage of labour and immediately after delivery
Pregnancy induced hypertension
Pre-eclampsia and eclampsia: defective placental implantation causing hypertension, proteinuria and oedema. Can result in disseminates intravascular coagulation, thrombocytopenia and hamorrhages.
Describe the mechanism of pre-eclampsia
There is defective invasion of the trophoblast. The trophoblast fails to invade and remodel the maternal endometrial spiral arteies which are necessary to increase blood flow to the placenta.
Placenta is poorly perfused and becomes ischemic and poorly developed. Hypoxia increases release of inflammatory mediators which damage the placenal and maternal endothelium.
Endothelial dysfunction increases vascular resistance. This further reduces placental blood flow (exacerbating placental ischemia) and causes maternal hypertension.
Renal arteriolar vasoconstriction simulates fluid retension and oedema, and causes glomerular damage resulting in proteinuria.
name 5 complications of preeclampsia
Blood: thrombocytopenia, coagulopathy
Altered vascular permeability: peripheral oedema, pulmonary oedema
Systemic vasoconstriction: hypertension
Placenta: fetal growth retardation, fetal hypoxia, placental abruption
Kidneys: proteinuria, renal failure
CNS: seizures, cortical blindness
What are the three classical symptoms of pre-eclampsia?
What is the treatment for pre-eclampsia?
Vasodilator to reduce bp
IV MgSO4 to reduce cerebral irritability and vasospasm (prevents fits)
Emergency caesarian section
Describe the respiratory adaptations that occur in pregnancy
Increase in maternal core temperature, which raises metabolic rate. O2 consumption increases (15%) to meet raised metabolic demands. This is facilitated by increased carrying capacity of blood.
Increase in sensitivity of chemoreceptors to CO2, increasing pulmonary ventilation by 40%. Tidal volume increases (more of inspiratory reserve volume used) ventilation rate is the same.
Changes all mediated by progesterone
What are the changes in blood gases in pregnancy?
Decreased pCO2 causes compensatory fall in HCO3. (mildly compensated respiratory alkalosis)
Arterial pH 7.4
How do the respiratory changes in pregnancy improve O2 delivery to the foetus?
The increased tidal volume causes a marked increase in ventilation. This enhances gas transfer.
pCO2 is reduced while pO2 is only marginally alteerd. This increases 2,3BPG, shifting the maternal dissociation curve to the right to maintain O2 saturation.
Increase in 2,3BPG reduces affinity of Hb for O2 and so also enhances transfer to fetal RBCs
How are the respiratory changes in pregnancy acheived?
Progesterone acts on the hypothalamus to increase metabolic rate and core temperature. The O2 carrying capacity of blood is increased to meet the demand. Progesterone also increases the sensitivity of chemorecptors to CO2. This increases pulmonary ventilation.
Levels of carbonic anhydrase in maternal RBCs are increased. (increased breakdown of CO2 and exrcretion of HCO3)
Describe the renal changes that occur in pregnancy
Increase in renal blood flow - increases GFR by 50%, creatinine clearance therefore increased by 50%. Low serum creatinine in pregnancy
Low urea and uric acid in early pregnancy - serum concentrations rise later in pregnancy due to increased tubular absorption
Increase in protein exrection
What are the renal complications of pregnancy?
Increased risks of UTI
Progesterone causes ureteric dilation and slowed urine input - can cause hydronephrosis, presents as loin pain. (can also result from mechanical obstruction of the ureter by the uterus)
Patients with impaired renal function may get worse
What are the effecs of diabetes on pregnancy?
Intrauterine growth restriction
What are the effects of pregnancy on diabetes?
Deterioration of renal function
Deterioration of opthalmic disease
What are the effects of diabetes on the fetus?
Maternal hyperglycaemia causes fetal hyperinsulinaemia in response.
There is increased foetal growth which can lead to:
- fetal macrosomia (risk of birth injury, shoulder dystocia)
- Polyuria/polyhydraminos (risk of preterm labor, malpresentation or cord prolapse
- Polycythemia due to increased oxygen demands (jaundice, thrombosis, risk of still birth)
- neonatal hypoglycaemia (risk of cerebral palsy)
Why is pregnancy diabetogenic?
The foetus has little capacity for gluconeogenesis because the enzymes required are deactivated at low O2. Glucose is therefore obtained from the maternal blood, and is dependent on maternal nutritional status
Progesterone increases maternal appetite and stimulates lipogenesis but also increases renal gluconeogenesis and protein breakdown.
hPL acts like growth hormone to mobilise fatty acids for maternal metabolism.
There is reduced insulin sensitivity due to the effects of hPL, oestrogen, progesterone and cortisol. This causes prolonged hyperglycaemia after eating, and reduced uptake of glucose by maternal tissues. More glucose is taken up by the placenta.
N.B. insulin release also increased relative to insensitivity
What is gestational diabetes?
Development of severe glucose intolerance in pregnancy
Name 4 risk factors for gestational diabetes
Poor obstetic history
Macrosomic infant in pregnancy
Weight > 100kg of BMI>30
South asian, middle eastern or african origin
How is thyroid function affected in pregnancy?
hCG has a high homology with TSH, and has a thyrotrophic function. This can increase the size of the thyroid gland.
Free concentrations of T3 and T4 stay the same because oestrogens stimulate the synthesis of thyroxine-binding globuln. Maternal bound T4 acts as a reservoir to supply the foetus with thyroid hormone.
What is the role of hPL in pregnancy?
human plcental lactogen is related to GH and PRL.
It alters maternal metabolism to make glucose more available to the foetus by antagonising the actions of insulin. This reduces glucose uptake in maternal cells raising maternal blood glucose (diabetogenic effect).
hPL increases proteolysis and lipolysis, providing more amino acids for foetus.
Promotes foetal growth by stimulating the production of IGFs.
How is calcium metabolism altered in pregnancy?
The total maternal Ca2+ falls due to reduced serum albumin.
PTH-related protein increases Ca2+ transport across the placenta. The fall in serum Ca2+ stimulates PTH output. This increases absorption of Ca2+ from the gut and kidney, and mobiisation of Ca2+ from the bone.
These mechanisms ensure that foetal serum Ca2+ remains high. If maternal dietary intake of Ca2+ is low, then Ca2+ is mobilised from bone and may contribute to dental caries in the third trimester.
What are the neuroendocrine adaptations that occur in pregnancy?
The maternal pituitary increases synthesis of:
prolactin (works with oestradiol and progesterone for breast development)
ACTH (important for priming myometrial activity, contributes to diabetogenic effect of pregnancy)
Oxytocin (synthesised and stored. Stimulates uterine contractions and milk ejection)
Name three haematological complications of pregnancy
How can pregnancy result in anaemia?
There is ~ 40% increase in plasma volume in pregnancy. Progesterone, hPL and PRL stimulate erythropoeisis but not enough to ofset the rise in plasma volume, therefore the haematocrit is diluted (physiological anaemia).
Pregnancy requires 1mg of iron (equivalent to total iron store). If mother is iron deficient or has low stores, it is likely that the she will have insufficient iron by the end of pregnancy (patients with a poor diet/vegans more at risk)
What are the effects of anaemia on pregnancy?
poor wound healing
heart failure/large blood loss at delivery
How can pregnancy result in thrombosis?
Pregnancy is pro-thrombotic
Stasis of blood due to venous compression by gravid uterus, immobility in labour, or due to illness e.g. pre-eclampsia/infection
Blood is hypercoagulable (increase in clotting factors e.g. fibrinogen, factor VII, VIII and X or dehydration)
Vascular damage e.g. varicose veins
What are the risk factors for developing thrombosis in pregnancy?
Abnormal clotting (APLS, thrombophilia)
How do you test for DVT?
Doppler ultrasound (measures blood flow and pressure in vessels)
How do you test for pulmonary embolism?
Radionuclide lung scan. Shows underperfused areas accompanied by a ventilation defect.
Pulmonary angiogram, shows filling defect
Significance of thombophilias in pregnancy
Associated with ayptical and arterial thrombosis, miscarriage, IUGR, pre-eclampsia, IUD, placental abruption
Desribe the immunological changes that occur in pregnancy
The maternal immune system is supressed to enable her to host the developing foetus. This predominantly affects cell-mediated immunity and susceptibility to viruses.
The placenta provides an immunological barrier for the foetus. The chorionic membranes are resistant to rejection as they lack the conventional HLAs, HLAC and HLAG are expressed by extravillous trophoblasts at the tip of invading spiral arteries.
IgG is transported across the placenta which confers passive immunity to the foetus against prevalent bacterial and viral infections (lasts 6 months).
State the changes that occur in maternal glucose metabolism to ensure foetal supply
Decreased overall maternal glucose concentration
Increased maternal insulin resistance
Increased maternal levels of alternate fuels (ketones, ffas, tgs)
Increased maternal insulin release in response to meals