Obs & Gynae - Physiological adaptations in pregnancy Flashcards
Before we learn all the conditions/ complications related to pregnancy, we must first understand what happens in the mother’s body during pregnancy i.e. what physiological changes (or adaptations) that help prepare the mum for pregnancy. These changes involves multiple organ systems, including the cardiovascular, respiratory, GI, MSK, endocrine, urinary, immunological and the haematological systems. It also causes changes in the uterus, vagina and breasts in pregnancy.
What is the hormone that causes most of these physiological changes? and What effect does this hormone have?
Progesterone - it relaxes smooth muscles everywhere in your body!
For example:
- LOS relaxes –> GORD
- Slower peristalsis in GI tract –> constipation and slower gastric emptying (early satiety)
- Dilatation of blood vessels –> low BP
(Here is just a few examples, but more will be discussed later for each system)
What physiological changes take place in the immunological system of the mother?
Physiological changes to the immunological system
The goal here is to induce physiological immunosuppression so that the mother’s immunity does not reject the baby, and also to confer passive immunity. The downside is an increased risk of infection during pregnancy
Changes include:
-
Th1 –> Th2 (cytokine) immunity, cell-mediated –> humoral immunity (antibodies predominate) to prevent rejection of the foetus
- Th1 cells secrete pro-inflammatory cytokines such as IFN-y and TNF-a, whereas Th2 cells secrete anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome
- Eczema is Th2-mediated, so it can get worse in pregnancy. However, Th1-mediated conditions e.g. psoriasis can improve
- hCG reduces maternal levels of IgA, IgG, and IgM –> physiological immunosuppression (which makes the pregnant woman susceptible to infections, hence why flu jabs are often given to them)
-
Confer passive immunity to the baby by transferring maternal antibodies (IgG) to the foetus just before birth
- However, autoantibodies can also be passed on and can cause things like Hashimoto’s and Grave’s
-
Switching of macrophages from M1 state (‘kill state’) to M2 state (‘repair state’) after establishment of an adequate placento-foetal blood supply
- The M1 state predominates around the time of implantation, switching to a predominantly M2 state once there is an adequate placento-foetal blood supply
- The thymus shows some reversible involution during pregnancy, caused by the progesterone-driven exodus of lymphocytes from the thymic cortex. Conversely, the spleen enlarges during pregnancy due to increased production of RBCs and immunoglobulin-producing cells. The lymph nodes in the para-aortic chain draining the uterus may increase in size
- Immunologically inert villous and extravillous trophoblast
- Release of transforming growth factor - beta 2, which has immunosuppressive activity, by granulated lymphocytes in 1st trimester
What physiological changes are seen in the uterus and the cervix during pregnancy?
Physiological changes to the uterus:
- Weight of the uterus increases: 100g (non-pregnant) –> 1000g (at term)
- Myometrial growth is almost entirely due to muscle hypertrophy and elongation of the cells from 50μm in the non-pregnant state to 600μm at term (although some hyperplasia may occur in early pregnancy) - due to the effect of the growing conceptus and oestrogens and progesterone
- _Despite the myometrial growth, the myometrium remains relatively **quiescent (maintained by progesterone) until the onset of labour_
- Progesterone maintains quiescence by increasing the resting membrane potential of the myometrial cells while impairing the conduction of electrical activity and limiting muscle activity to small clumps of cells. Hence, progesterone antagonists e.g. mifepristone can induce labour from the 1st trimester, as can prostaglandin F2α, which is luteolytic (tho oxytocin is the 1st line medication to induce labor)
- The uterine cavity expands from 4mL to 4000 mL at full term - this reflects a much greater compliance in the pregnant myometrium compared to that of non-pregnant myometrium. Therefore, although the uterus is distended by the growing foetus, the intrauterine pressure remains constant!
- _Despite the myometrial growth, the myometrium remains relatively **quiescent (maintained by progesterone) until the onset of labour_
- Retroverted uterus (backward tipping of the uterus towards the rectum) may lead to retention (12-16 wks), usually self corrects - see image in the question card
-
Braxton-Hicks contractions - these are non-painful ‘practice contractions’ late in pregnancy (>30 wks)
- Often described as feeling like mild menstrual cramps or a tightening in a specific area of the stomach that comes and goes
- More frequent and intense Braxton Hicks contractions can signal pre-labor
-
Changes in the cervix - its function is to retain the conceptus
- Increased vascularity
- Hypertrophy of the cervical glands producing the appearance of a cervical erosion (also called cervical ectropion)
- An increase in mucous secretory tissue in the cervix during pregnancy leads to a thick mucus discharge and the development of an antibacterial plug of mucus in the cervix
-
Reduced collagen in the cervix in the 3rd trimester (a 1/3rd reduction of collagen fibres) and the accumulation of glycosaminoglycans and water lead to characteristic changes of cervical ripening/ effacement (softening of the cervix prior to the onset of labor contractions and is necessary for cervical dilation and the passage of the foetus):
- The lower section shortens as the upper section expands, while during labour there is further stretching and dilatation of the cervix - see image
-
Stretching and thinning of the uterus isthmus (a junctional zone between the cervix and the body of the uterus) due to regular contractions by the 28th week of gestation, resulting in early formation of the lower uterine segment. The lower uterine segment doesn’t really contribute to the expulsive efforts of the uterus, rather, it becomes an extension of the birth canal
- Due to its relative avascularity and quiescence (inactivity) in the puerperium (6 week period after childbirth), the lower uterine segment is the site of choice for the incision for a caesarean delivery
-
Hypertrophy of blood vessels supplying the uterus - driven by progesterone –> a massive increase in uterine blood flow from 50 mL/min at 10 weeks’ gestation to 500-600 mL/min at term
- The uterine arteries dilate - diameters are 1.5 times those seen outside pregnancy
- The arcuate arteries, supplying the placental bed, become 10 times larger, and the spiral arterioles reach 30 times the pre-pregnancy diameter
-
Remodelling of the spiral arteries (discussed more later) - this is very important as failure of this process can cause pre-eclampsia and intrauterine growth restriction
-
What physiological changes are seen in the vagina during pregnancy?
- Hypertrophy of the stratified squamous epithelium lining the vagina and the musculature in the vaginal wall
- Collagen decreases while glycosaminoglycans and water increase
- The venous vascular network in the vaginal wall becomes engorged –> slightly bluish appearance
- A fall in vaginal pH in pregnancy to 3.5-4.0 (normal vaginal pH is < 4.5), and this acid environment keeps the vagina clear of bacterial infection
- This is due to high oestrogen levels stimulating glycogen synthesis and deposition in epithelial cells, and as these epithelial cells are shed into the vagina, lactobacilli break down these glycogen to produce lactic acid! However, candida infections are common in pregnancy
Cardiovascular system
a) . Why is there a need for the cardiovascular system to make adaptations for pregnancy?
b) . What are the physiological changes to the cardiovascular system in pregnancy? Please justify your answer
c) . Why is it important to monitor BP in pregnancy?
d) . What ECG changes can you see in pregnancy?
a). There is an increase in oxygen demand in pregnancy due to:
- The growing foetus which has its own increasing oxygen demands to meet
- Increasing size of the uterus and increasing maternal metabolic rate
- Rapidly growing myometrium –> increased demand for nutrients (O2, glucose …) –> need more blood supply to sustain its activity
The physiological changes in the maternal CVS occur in order to increase delivery of oxygenated blood to the tissues and the foetus
b). Physiological changes to the cardiovascular system: (see image attached for a summary of CVS changes)
-
TPR decreases –> low BP (systolic BP unchanged, only the diastolic BP reduced) - due to progesterone causing vasodilation, reducing the afterload. Other vasodilators involved in early gestation include prostacyclin (PGI2) and NO and, later, ANP. There is also a loss of pressor responsiveness to angiotensin II
- The BP falls during the 1st and 2nd trimester but normalises in T3
c). To rule out conditions like pre-eclampsia (high BP) and intrapartum haemorrhage (very low BP)
- To compensate for a fall in TPR, the SV and HR increases –> CO increases
- BP = CO x TPR so if TPR falls CO increases to compensate so the BP won’t fall too low
- Half of the total increase in CO occurs by 8 weeks of gestation. CO peaks at 16 weeks, and during labour (often tachycardic due to the pain and increased expulsive efforts) and postpartum
- Blood volume increases –> EDV in the LV (preload) increases - due to activation of the RAAS in pregnancy leading to an increased Na+reabsorption and water retention
- Physiological mild LV hypertrophy that goes away after pregnancy - this is due to an increased CO, the heart working more causing muscle hypertrophy
- Displaced apex beat due to the diaphragm pushing upwards rotating the cardiac axis to the left, so the apex of the heart is displaced upwards and left laterally (left axis deviation)
-
Progressive venodilatation and increase in venous distensibility and capacitance (increased venous pooling). The CVP and pressure in upper arms remain constant in pregnancy, but the venous pressure in the lower circulation rises progressively on standing, sitting or lying supine because of pressure from the gravid uterus in late pregnancy
d) . Physiological ECG changes: - Atrial and ventricular ectopics
- Left shift of QRS
- Inverted T-wave in lead III and a q-wave in leads III and aVF
- ST depression and T-wave inversion in inferior and lateral leads
How does BP changes throughout pregnancy?
BP falls during the 1st and 2nd trimester and normalises in the 3rd trimester
(see image)
a) . What times throughout gestation are women with pre-existing heart disease e.g. aortic stenosis at most risk?
b) . How does aortic stenosis put a pregnant woman at risk of cardiac arrest during delivery?
a) . The time when the CO is at its highest (peaks at 16 weeks, during labour and postpartum), that’s when women with pre-existing heart disease are at most risk!
b) .
* The woman loses a lot of blood during delivery, this means that there will be less blood going back to the LV amd less blood being pumped into the systemic circulation
* If the blood flowing into the systemic circulation is already low in a woman who just went to labour, an aortic stenosis would cause an even lower blood volume going into the circulation, so you get less perfusion of tissues including the heart and the brain, so the mother can get cardiac arrest post-partum
***PREGNANCY IMPOSES A SIGNIFICANT INCREASE IN CARDIAC OUTPUT AND IS LIKELY TO PRECIPITATE HEART FAILURE IN WOMEN WITH PRE-EXISTING HEART DISEASE!!!! (take home message)
Why may a profound fall in BP occur in late pregnancy (3rd trimester) when the mother lies on her back?
What is the name of this phenomenon?
How do you manage it?
This phenomenon is known as the supine hypotension syndrome (also called aortocaval compression syndrome). It results from the restriction of venous return from the lower limbs due to compression of the IVC and hence a fall in SV.
Aortic compression also occurs and this will result in big differences between brachial and femoral BP in pregnancy and radio-femoral delay
Mx - Get her to lie on the side to relieve the obstruction (see image)
Respiratory system
What are the physiological changes to the respiratory system in pregnancy?
Physiological changes to the respiratory system:
- Increased basal metabolic rate (BMR) –> Increased oxygen demand (or requirement)
-
Increased minute ventilation rate (MV) secondary to an increased tidal volume (TV) with a stable RR
- MV = TV x RR
- Increased alveolar ventilation secondary to increased respiratory drive (hyperventilation) driven by progesterone (sensitizes the medulla oblongata where the respiratory centre is found) –> physiological dyspnoea
- This hyperventilation leads to an increase in arterial pO2 and a decrease in arterial pCO2, resulting in respiratory alkalosis with a compensated increase in renal bicarbonate excretion. Therefore, the arterial pH remains constant
- CO2 production increases sharply in the 3rd trimester as foetal metabolism increases. The low maternal pCO2 allows more efficient placental transfer of CO2 from the foetus
- The increase in arterial pO2 shifts the maternal oxygen dissociation curve to the right due to an increase in 2,3-DPG in the RBCs, this allows a more efficent O2 unloading to the foetus
- This hyperventilation leads to an increase in arterial pO2 and a decrease in arterial pCO2, resulting in respiratory alkalosis with a compensated increase in renal bicarbonate excretion. Therefore, the arterial pH remains constant
- Upward displacement of the diaphragm due to the gravid uterus –> reduced FRC and RV but an increased inspiratory capacity. However, the vital capacity and the total lung capacity remain unchanged as there is also an increase in the transverse and anterior-posterior diameters of the thorax
-
PEFR and FEV1 remain unchanged - this is important as it allows you to monitor their asthma during pregnancy
- Women with asthma do not appear to be affected by pregnancy
Gastrointestinal system
What physiological changes are seen in the GI system of a pregnant woman?
Physiological changes to the GI system:
- Progesterone causes smooth muscle relaxation:
-
Slower peristalsis –> constipation and bloating (though this allows for more time for nutrient absorption)
- This is exacerbated by the gravid uterus compressing on the GI tract
- Relaxation of the LOS –> GORD and heartburn
- This is exacerbated by the upward displacement of the stomach as the uterus grows and also morning sickness secondary to a raised hCG –> GORD and N&V
- Stasis of bile in the gallbladder –> gallstone formation –> travel down the biliary tract –> acute pancreatitis
-
Slower peristalsis –> constipation and bloating (though this allows for more time for nutrient absorption)
- Viscera displaced due to the foetus – e.g. appendix moves to right upper quadrant
- Hepatic synthesis of albumin, plasma globulin and fibrinogen increases under oestrogen stimulation - the latter two increase sufficiently to give increased plasma concentrations despite the increase in plasma volume
- Hepatic blood flow doesn’t change; ALP raised 50% and albumin levels fall
- The albumin falls due to the increased plasma volume despite an increased synthesis of albumin from the liver
- Hepatic blood flow doesn’t change; ALP raised 50% and albumin levels fall
Urinary system
What physiological changes would you see in the urinary system of a pregnant woman?
Physiological changes to the urinary system:
- GFR increases (by 50%) - due to increased CO causing an increase in renal plasma flow and also progesterone-driven vasodilation of the afferent arteriole
- Renal blood flow increases - due to progesterone causing vasodilation and also an increase in CO
- Increased renal excretion due to an increased GFR –> Increased glycouria, proteinuria, bicarbonaturia, calciuria. creatininuria and urea excretion
-
Plasma osmolarity decreases - since plasma proteins and other solutes are filtered leading to a decreased oncotic pressure
- This is clinically significant as it can cause peripheral oedema (swelling of ankle, leg, feet), which is often made worse by the gravid uterus compressing on the IVC, as it reduces venous return and causes blood to pool in the venous capillaries –> varicose veins in lg
- Filtration capacity intact
- Functional renal reserve decreases as GFR increases
- Increased renin (due to low BP causing RAAS activation –> increased Na+ and water reabsorption), EPO (increases RBC production in preparation for blood loss during labour) and active vitamin D production (to increase calcium absorption in the intestine since there is increased calciuria)
- Progesterone causes smooth muscle relaxation in the ureters and the bladder –> urinary stasis in the ureters (hydroureters) and bladder –> UTIs and pyelonephritis (as urine backflows into the kidneys causing hydronephrosis). This is exacerbated by the baby compressing on the bladder –> LUTS (frequency, urgency, nocturia …)
- Weakness of the bladder can also cause urinary incontinence in pregnant women
Haematological systems
What physiological changes are seen in the haematological systems in pregnancy?
Physiological changes to blood in pregnancy:
-
Increased maternal blood volume (up 30%) mostly in the 2nd half
- The plasma volume increases significantly (up 50%) but the red cell mass does not increase by much (only up 20%) –> lower HCT –> physiological dilutional anaemia
- Treat with iron supplement e.g. ferrous sulphate with vitamin C
- The plasma volume increases significantly (up 50%) but the red cell mass does not increase by much (only up 20%) –> lower HCT –> physiological dilutional anaemia
- Increase in coagulant activity –> prothrombotic state –> this helps to prepare for blood loss during delivery
- Increased fibrinogen and clotting factors production (particularly factor VII, VIII, IX and X whereas factor II and V remain constant)
- Increased fibrin deposition at implantation site
- Decreased fibrinolysis - this returns to normal after delivery
- Exacerbated by progesterone as it can cause stasis of blood and ventilation
- All of the above increases the risk of thromboembolism in pregnancy
- To reduce the risk, LMWH is usually considered in pregnancy if it’s necessary to give the mother an anticoagulant drug
- _*****Warfarin is CONTRAINDICATED as it’s teratogenic_
- Anaemia due to iron and folate deficiencies can also occur
-
Increased total WCC and ESR
- Mainly due to an increase in neutrophil polymorphonuclear leukocytes that peaks at 30 weeks gestation. A further massive neutrophilia normally occurs during labour and immediately post delivery
- A significant fall in platelet count - maybe due to a dilutional effect, but the substantial increase in platelet volume from 28 weeks suggests that there is increased destruction of platelets in pregnancy with an increase in the number of larger and younger platelets in the circulation
Which medication is used to induce labour?
Oxytocin (the synthetic version is Syntocinon) is used to induce labour. It can also be used in the active Mx of the 3rd stage of labour as it causes uterus to contract
How do you treat antiphospholipid syndrome in pregnancy?
Which antibody will raise in antiphospholipid syndrome?
Low dose aspirin + Low dose LMWH
Elevated anticardiolipin antibody
Endocrine system
What are the physiological changes to the endocrine system in pregnancy?
Physiological changes to the endocrine system:
Placenta
- Secretes large amounts of oestrogen and progesterone, both being needed for uterine growth and quiescence and for breast development
- Oestrogen increases the production of cortisol-binding globulin (CBG) and thyroid-binding globulin (TBG) throughout pregnancy
- Increased relaxin - relaxes the cervix and pelvic ligaments in preparation for childbirth
Pituitary gland
- Anterior pituitary
-
Increased prolactin secretion due to stimulation by oestrogen
- There is a steady rise in prolactin synthesis and plasma concentration, with a surge at the time of delivery, and a subsequent fall with the disappearance of placental oestrogens. Levels of prolactin remain elevated above basal in women who continue to breastfeed
- Note that during pregnancy, even though prolactin level is high there is little milk production because oestrogen inhibits the stimulatory effects of prolactin. However, after delivery the massive drop of oestrogen allows prolactin to induce lactation
-
Increased ACTH and cortisol level (due to a raised CRH) but they remain within the normal non-pregnant range due to an increased CBG
- Increased cortisol level enhances the catabolic effect on energy reserve, more glucose is available for the baby
- GnRH, LH, FSH, TSH and GH are inhibited by the rising hCG level
-
Increased prolactin secretion due to stimulation by oestrogen
- Posterior pituitary
- Increased ADH production–> a fall in plasma osmolality in early pregnancy. However, this later normalises as the level of placentally produced leucine aminopeptidase (PLAP) increases
-
Oxytocin levels remain low during gestation due to high concentrations of PLAP and are not raised in labour. However, there is an upregulation of uterine oxytocin receptors, so there is enhanced sensitivity to oxytocin - this is due a high oestrogen: progesterone ratio, as oestrogen upregulates binding sites and progesterone downregulates them
- Oxytocin causes:
- Milk ejection in let-down reflex of breastfeeding, following stimulation of the nipples (discussed more later)
- Uterine contractions and dilation of cervix in labour
- Oxytocin causes:
Thyroid gland:
- Increased total T3 and T4 as a result of the increase in TBG
- Free T4 in the normal range
- TSH level decreased due to inhibition by the rising hCG level
Breast development during pregnancy
What are the physiological changes to the breast during pregnancy?
Physiological changes to the breast:
- Signs and symptoms of pregnancy: breast tenderness, increase in size, enlargement of the nipples, and increased vascularity and pigmentation of the areola
- The areola contains sebaceous glands that hypertrophy during pregnancy (Montgomery’s tubercles) - see image
- High oestrogen levels stimulate ductal proliferation during pregnancy
- Alveolar growth is stimulated by progesterone and prolactin
- Note that full lactation is inhibited during pregnancy by the high levels of oestrogen and progesterone that block the alveolar transcription of α-lactalbumin.
Describe the circuitry of lactation, with reference to oxytocin and prolactin
Baby sucks nipple –> signals sent to the hypothalamus –> hypothalamus stimulates the anterior pituitary to secrete prolactin (by inhibiting the release of dopamine which is a prolactin-inhibiting hormone) –> _prolactin is secreted *during* and *after* feed to produce *next* feed_
High prolactin level –> negative feedback to the hypothalamus –> inhibits GnRH secretion –> suppresses ovulation thus no menstruation
At the same time, baby sucking on the nipple also causes the posterior pituitary gland to secrete oxytocin by the hypothalamus. Oxytocin causes contraction of the myoepithelial cells in the mammary glands, ejecting milk (‘let-down’ reflex). Just like prolactin, oxytocin will cause a negative feedback on the hypothalamus, causing a fall in GnRH, inhibiting the ovarian cycle!
