13 maternal adaptation to pregnancy Flashcards
which hormones have a higher plasma level in pregnancy than luteal phase?
does this affect the fetus?
progesterone- corpus luteum and then placenta; 200mg/ day by late pregnancy
oestrogen- co-operation of placenta and fetus
no:
- placental polarity: prevent too much progesterone and oestrogen
- fetus can conjugate steroids to sulfates making biologically inactive
pregnancy hormones
- placental prolactin (breast changes, behavioural changes)
- placental lactogens (maternal insulin and glucose metabolism, lipolysis, erythropoiesis)
- CRH from placenta-> increased secretion of cortisol in mother Too high levels affect nutrient transfer and placental clock (risks: pre-term labour, early parturition signals) Male fetus respond more acutely to cortisol levels from mum
- aldosterone (plasma volume)
- erythropoietin (RBC)
- Cytokines- pro inflammatory, interleukins, TGF- beta
- Vasodilatory mediators: VEGF, NO (vasodilation, angiogenesis)
muscular anatomical changes
- uterine enlargement (expands and increases in weight x20)
- hypertrophy of uterine musculature: expulsion of fetus at partruition
- quiesence of myeometrial contractions during gestation
- prostaglandin and oxytocin stimulate - diaphragm displaced cranially by gravid uterus (4cm elevation)
cardiovascular anatomical changes
- apex of heart moves anterior and to left (pushed upwards and rotates forwards)
- LV hypertrophy - cope with increased CO (not permanent
other anatomical changes in pregnancy
- changes in calcium conc in maternal bones ( increased intestinal calcium absorption maternal bone loss may occur in trimester and lactation- reversible)
- Decidual changes in endometrium to accommodate growing baby
- Development of mammary glands to form lactating breast
- Weight gain due to increase maternal blood volume and weight of placenta and baby
cv system: Blood volume and haematological indices
changes in:
blood volume
RC mass
haematocrit and hb
hb values at term
- Increase in blood volume throughout pregnancy: 40% increase by full term (over a litre)
- Red cell mass increases linearly (30%)
- Plasma volume increases > cell mass so there is a fall in hematocrit and haemoglobin
Advantage: decreased viscosity -> reduced resistance in flow; better placental perfusion
- At term: hb values 50%> non pregnant
- Useful protection blood loss at delivery, 500ml placental maternal blood goes back to mum during delivery
mechanisms of blood volume and haematological indices changes
what is important during pregnancy?
Hormonal stimulation:
- stimulation RAAS: aldosterone leading to sodium ion and water retention-> increased plasma volume
- increased renal erythropoetin: increases red cell mass
supplement iron and folic acid levels to help restore hb levels
CV system: Total peripheral resistance in pregnancy
factors
changes in vascular tone
- Angiogenic, permeability and vasoactive factors: VEGF (permeability), PLGF, NO and progesterone (relaxes arterial smooth muscles)
- Vascular dilatation and relaxation of peripheral vascular tone
- New vascular beds (angiogenesis in mum too), including utero-placental circulation -> drop in peripheral resistance
- Lowers blood pressure (contributes to increased blood volume)
->reduction in peripheral vascular resistance
Reduces about 40% in mid-pregnancy, rising slowly to term
CV system: cardiac output
- increase in blood volume= more blood enters heart -> increased preload
- decrease in peripheral resistance due to vasodilatation-> reduced afterload
- increase in stroke volume
- increase in maternal heart rate
- increase in CO (SV x HR)
why is an increase in CO needed in pregnancy?
extra 30-50ml oxygen consumed per minute
- blood flow to uterus and placenta: 25% maternal CO
- CO does not fall towards term
how much can CO increase during labour
2L/min
what is the blood pressure like during pregnancy?
BP= CO X resistance
Systolic bp stable in pregnancy.
In early pregnancy, diastolic pressure does not fall reaching a nadir at around 20 weeks, rises to normal by term
ECG changes during pregnancy
leftward deviation of 15 degrees. Flattening/inversion of T wave in lead III; ST segment depression.
what does enlarging uterus cause when mother lies supine
IVC and aorta compression
what happens if IVC is compressed?
- reduces venous return to heart (fall in pre- load and CO)
- Resultant fall in bp- can be severe for loss of consciousness
what happens if the aorta is compressed
- reduces uteroplacental and renal blood flow
- Last trimester: maternal kidney function lower in supine than lateral position
- Fetal transplacental gas exchange may be compromised
respiratory system: structural changes
increased chest expansion, displaced diaphragm, increases vascularisation of upper respiratory tract
respiratory system: ventilatory adaptations
- Progesterone- mediated hypersensitivity to CO2 increases RR by 15%
- Tidal volume by 40%
- Alveolar ventilation- 70% higher at end of gestation
fall in arterial and alveolar CO2 tensions: 4.1 kPa by end of first trimester (25% decrease). PaO2 increases to 13-14 kPa
respiratory system changes: consequences to baby
- Higher PaO2 on maternal side of placenta facilitates oxygen transfer to fetus
- Lower PaCO2 facilitates transfer of CO2 in reverse direction
maternal renal function: anatomical changes
- Kidneys enlarge (1cm increase in size) due to increased vasculature, vascular dilatation and interstitial space increases
- Renal parenchymal volumes increase in pregnancy, glomerular (Bowman’s capsule) diameters are greater
- Dilatation of calyces, renal pelvis and ureter (progesterone and local pressure effect)- increases chance UTI
- Bladder loses tone: increased urinary freq and urgency
maternal renal function: physiological changes
- Increase RPF, decrease renal vascular resistance
- Changes in GFR and GFF (filtration fraction)
- Changes in tubular re-absorption
renal haemodynamics alterations in pregnancy
FF= GFR/ RPF
- RPF increases 50-80% between conception and mid pregnancy (and then decreases in third trimester)
- GFR increases but less than RPF
-> FF declines in early pregnancy
Non pregnant state FF= 20%. Similar to late pregnancy
changes in glucose handling
FF declines, increased renal flow-> more glucose in filtrate.
- Filtered load of glucose rises in pregnancy and exceeds maximal rate of reabsorption
- Urine is not glucose free
- Excretion can be 10x higher than non pregnant
- Glycosuria
- Increased chances of UTI
what determines fetal glucose levels
maternal glucose levels
net flux of glucose from mother to fetus (fick’s principle)
Increase glucose excretion in mother- is there a glucose deficit in the mother?
evidence for:
- Fasting blood glucose 10mg/dl lower than non- pregnant
- Ketones found in maternal blood
‘accelerated starvation’
evidence against
- Fasting hypoglycaemia in first trimester, decrease in glucose levels reach nadir around 12 weeks gestation
- Then reverts to normal in second and third trimester
how do glucose levels revert to normal in early pregnancy?
- Progesterone increases maternal appetite (and stimulates deposition of glucose in fat stores)
- Increased insulin secretion- favours lipogenesis and storage of fat
how do maternal levels revert to normal in mid pregnancy? (5)
- Increased absorption of glucose from gut
- Increased maternal gluconeogenesis and total glucose production (glycogenolysis)
- Mobilisation of FFA and lipolysis (influenced by placental lactogen)
- Enhanced lipolysis- increases FFA and oxidation and ketones. Alternative fuel used by mother, thus reducing own need for glucose- spared for fetus
- Maternal tissue becomes progressively insulin insensitive (50-80% decline in insulin sensitivity in skm).
- Development mild insulin resistance
- Decrease uptake of glucose by maternal tissue
- After 20 weeks, plasma glucose levels are normal
Conflict with concept of pregnancy being example of accelerated starvation
explain response to glucose load in post pregnant and third trimester (38 weeks)
post pregnancy:
- plasma glucose reaches peak 30mins after ingestion
- returns to baseline after 60 mins
third trimester:
- plasma glucose slower to reach peak
- peak is higher (*)
- returns to baseline after 2h
Prolonged duration of postprandial hyperglycaemia in pregnancy
insulin levels in response to glucose load- last trimester
- Higher glucose peak-> higher insulin secretion
- Insulin reaches peak after 1h (*)
- Declines slowly but not back to basal levels in pregnancy (vs post pregnant values)
Postprandial hyperinsulinmea. Evidence of insulin resistance
is increased insulin resistance a cause of GDM
possible cause
- Initially silent period begins as insulin gets higher (2nd trimester), silent period when most damage is done
resistance also higher in maternal obesity
immunulogical role of placenta
(fetus has MHC and macrophages)
- structural barrier stopping direct contact of maternal blood with the fetus
- Fetus has major histocompatibility antigens (MHCs), but placenta, specifically syncytiotrophoblast surface does not. Acts as immunological barrier
- Fetus hides behind placenta
- Syncytial structure of syncytiotrophoblast (SN)- maternal immune cells cannot cross to the fetus without going through cytoplasm and being downgraded (lyosomal system)
- If they transcytose to placental stroma, fetal macrophages (Hofbauer cells) phagocytoses maternal immune cells
how does fetus avoid rejection?
- Syncytial knots, exosomes, cell free DNA, fetal stem cells shed into maternal circulation are phagocytosed by maternal immature dendritic cells
- Phagocytosed debris contains intracellular fetal HLA (Class I & II)
- These fetal peptides presented by maternal dendritic cells to T cells in endometrium
- Induces a) t cell apoptosis and b) conversion to T reg suppressor cells (avoid high levels of T cells)
Peripheral tolerance of fetal HLA develops. Tolerance by the maternal immune system is achieved (changing maternal ‘self’ hypothesis)
immune function of endometrium
- Endometrial mucosa is an immunologically privileged site
- Must mount immune response against microorganisms and be able to tolerate sperm and allogenic fetus
- No trafficking of endometrial lymphocytes to other mucosa
- Under influences of pregnancy hormones, T helper cells decline relative to suppressor cells or Treg in endometrium
- Treg act to decrease immune function. Suppresses response from dwindling t cells and help maintain materno-fetal tolerance
immune cells in endometrium
Dendritic (APC) cells
Th cells
T reg cells
Uterine NK cells
Mechanisms of tolerance at fetal-maternal interface
Soluble factors may provide local immunoprotection of fetus
- Secretion of endometrial glycoproteins by decidual stromal cells suppress uterine NK cells. uNK cells produce cytokines kill fetal cells
- Secretion of placental galectins- immunosuppressive
- Production of anti-inflammatory factors: TGF-b and IL-10 by the decidua and the placenta aids apoptosis of T cell and their conversion to T reg.
Extra-villous trophoblast cells (EVTs)- invade endometrium and remodel spiral arteries, lack conventional class I and II MHCs
- Unique HLA class I antigens: HLA-C,-G and -E
- HLA-G is not expressed in any other maternal or fetal cells
what is the role of Invading EVTs
- uNK contain killer cell immunoglobulin-like receptors
- can recognise HLA-G on invading trophoblast cells
- binding of HLA-G with KIR on uNK inhibits cytokine production by uNK (negative signal)
- inhibits uNK cells capacity to secrete cytokines which cause fetal cell lysis, thus controlling maternal immune response
acquired immunity: can cell transfer of maternal igG become a problem?
what is the role of MHC I IgG
supress immune reactions
