Physiology of pregnancy

Question 1

Name 4 maternal symptoms in early pregnancy

Answer 1

Nausea Constipation Lethargy Breast tenderness

Question 2

Name 4 unwanted effects of progesterone during pregnancy?

Answer 2

Constipation Reflux Oedema Progesterone + mechanical: Haemorrhoids Flushes

Question 3

What is the basis of pregnancy testing?

Answer 3

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

Question 4

Describe the cardiovascular changes that occur in pregnancy

Answer 4

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

Question 5

Describe how cardiovascular changes during pregnancy are acheived

Answer 5

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.

Question 6

Why will a bp measurement taken from a pregnant woman in the supine position be innacurate?

Answer 6

Supine hypotension.

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%)

Question 7

How can pregnancy result in varicose veins?

Answer 7

Pressure of the gravid uterus on the vena cava can restrict venous drainage from the legs, damaging the valves in the veins.

Question 8

Describe the cardiovascular changes that occur in labour

Answer 8

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

Question 9

Describe the cardiovascular changes that occur after delivery

Answer 9

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

Question 10

What are the symptoms of the haemodynamic changes in pregnancy?

Answer 10

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.

Question 11

Describe the changes in blood pressure that occur in pregnancy

Answer 11

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,

Question 12

What are the common cardiovascular complications of pregnancy?

Answer 12

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.

Question 13

Describe the mechanism of pre-eclampsia

Answer 13

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.

Question 14

name 5 complications of preeclampsia

Answer 14

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

Liver: haemorrhage

Question 15

What are the three classical symptoms of pre-eclampsia?

Answer 15

Proteinuria

Hypertension

Oedema

Question 16

What is the treatment for pre-eclampsia?

Answer 16

Vasodilator to reduce bp

IV MgSO4 to reduce cerebral irritability and vasospasm (prevents fits)

Emergency caesarian section

Question 17

Describe the respiratory adaptations that occur in pregnancy

Answer 17

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

Question 18

What are the changes in blood gases in pregnancy?

Answer 18

pO2 increases

pCO2 decreases

Decreased pCO2 causes compensatory fall in HCO3. (mildly compensated respiratory alkalosis)

Arterial pH 7.4

Question 19

How do the respiratory changes in pregnancy improve O2 delivery to the foetus?

Answer 19

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

Question 20

How are the respiratory changes in pregnancy acheived?

Answer 20

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)

Question 21

Describe the renal changes that occur in pregnancy

Answer 21

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

Glycosuria (physiological)

Increase in protein exrection

Question 22

What are the renal complications of pregnancy?

Answer 22

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

Question 23

What are the effecs of diabetes on pregnancy?

Answer 23

Miscarriage

Fetal malformations

Intrauterine growth restriction

Macrosomia

Unexplained IUD

Pre-clampsia

Question 24

What are the effects of pregnancy on diabetes?

Answer 24

Poorer control

Deterioration of renal function

Deterioration of opthalmic disease

Gestational DM

Question 25

What are the effects of diabetes on the fetus?

Answer 25

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)

Question 26

Why is pregnancy diabetogenic?

Answer 26

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

Question 27

What is gestational diabetes?

Answer 27

Development of severe glucose intolerance in pregnancy

Question 28

Name 4 risk factors for gestational diabetes

Answer 28

Family history

Poor obstetic history

Significany glycosuria

Plyhydroaminos

Macrosomic infant in pregnancy

PCOS

Weight > 100kg of BMI>30

South asian, middle eastern or african origin

Question 29

How is thyroid function affected in pregnancy?

Answer 29

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.

Question 30

What is the role of hPL in pregnancy?

Answer 30

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.

Question 31

How is calcium metabolism altered in pregnancy?

Answer 31

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.

Question 32

What are the neuroendocrine adaptations that occur in pregnancy?

Answer 32

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)

Question 33

Name three haematological complications of pregnancy

Answer 33

Anaemia

Thrombosis

Thrombophilias

Question 34

How can pregnancy result in anaemia?

Answer 34

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)

Question 35

What are the effects of anaemia on pregnancy?

Answer 35

tiredness

breathlessness

poor wound healing

heart failure/large blood loss at delivery

Question 36

How can pregnancy result in thrombosis?

Answer 36

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

Question 37

What are the risk factors for developing thrombosis in pregnancy?

Answer 37

Immobility

Dehydration

Abnormal clotting (APLS, thrombophilia)

Older age

Obesity

varicose veins

Question 38

How do you test for DVT?

Answer 38

Doppler ultrasound (measures blood flow and pressure in vessels)

Question 39

How do you test for pulmonary embolism?

Answer 39

Radionuclide lung scan. Shows underperfused areas accompanied by a ventilation defect.

Pulmonary angiogram, shows filling defect

Question 40

Significance of thombophilias in pregnancy

Answer 40

Associated with ayptical and arterial thrombosis, miscarriage, IUGR, pre-eclampsia, IUD, placental abruption

Question 41

Desribe the immunological changes that occur in pregnancy

Answer 41

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).

Question 42

State the changes that occur in maternal glucose metabolism to ensure foetal supply

Answer 42

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