pregnancy Flashcards
describe the phyiological changes that occur in pregnancy
can be described by system and in time order. ALL occur to support developing fetus and prepare mum for birth and breast feeding.
governed by hormonal changes - bHCG, progesterone, oestrogen, human placental lactogen.
and also the mechanical effects of the fetus…
AIRWAY
* upper airway engorgement for tissue oedema (progesterone) - may need smaller tube
* breasts pushed up and shorted neck may make positioning hard and difficult aiway risk
BREATHING
* reduced FRC from gravid uterus and larger breasts
* closing capacity may encroach FRC - shunting, hypoxaemia
* bronchial smooth muscle relaxation (progesterone) - reduced resistance, increased deadspace.
* increase in TV and RR by term and hence MV
CARDIO
* progesterone dilates vessels - drop in SVR - both systolic BP and diastolic drop but systolic more - widened pulse pressure.
* increased CO - due to increase HR, SV and drop in SVR. and increased blood volume increases preload. increases all way up to delivery.
* aortocaval compression - compression of IVC and aorta by gravid uterus can reduce preload/ cardiac output - left lateral tilt to avoid this.
NEURO
* reduced epidural and intrathecal space - due to venous engorgement from aortocaval compression from gravid uterus - hence need less anaesthetic needed and higher risk of catheter becoming misplaced.
* higher sympathetic tone in pregnancy helps to counter effects of progesterone. however when sympathetic blocked in spinal, can see a big drop in BP
* MAC reduced
RENAL:
* increased blood flow and therefore GFR (150ml/hr)
* increased urine volume - drop in plasma urea and creat
* hence T max redcued for glucose - glucosuria is normal.
* progesterone relaxes ureters - increased stasis and infection risk.
GASTRO:
* reduced LOS tone and increased gastric pressure - more risk of reflux and aspiration
* hence commonly use antacids in labour and RSI
* returns to normal 48 hours after labour
LIVER:
* reduced production of plasma cholinesterases and albumin - affects pharmacokinetics
* increased gallstone risk
HAEM
* increased plasma volume - secondary to RAAS simulation and fluid retention
* red cell volume falls initially then increases back to normal by 16 weeks and then above normal by term. due to EPO increase
* however the above are disproportionate i.e. red cell volume increases less than plasma hence drop in haematocrit and physiological anaemia
* neutrophilia is seen
* hypercoaguable state - increased fibrinogen and clotting factors.
ENDO:
increased levels of corticosteroids
risk of sheehans syndrome at birth
changes to insulin production to counter anti-insulin hormones of fetus - risk of gestational diabetes.
what happens to compliance of lungs in pregnacy?
chest wall compliance reduced
lung compliance no change
overall reduced.
what happens to blood gas in pregnancy?
fall in PaCO2 due to alveolar hyperventilation - resp alkalosis
drop in bicarb to compensate
PaO2 may be higher as well due to lower PaCO2 - as per alveolar gas equation.
what happens to pulmonary vascular resistance in pregnancy?
drops
progesterone
what is vena cava compression syndrome seen in pregnancy?
compression of vena cava
drops preload and hence CO
sweating , pallor, drop in BP , nausea
can also cause fetal distress if cardiac output drops
describe change in CO throughout pregnancy and at delivery
even at birth there is an increase
as the uterine contraction and delivery of placenta results in return of 500ml of blood to systemic circulation - hence increased preload.
what murmur may be normal in pregnancy?
systolic murmurs
LV hypertrophy
can you describe some hormonal changes seen in pregnancy?
bHCG - early secreted from placenta, maintains corpus luteum for progesterone secretion
human placental lactogen - growth of fetus and breasts, decreases insulin sensitivity to promote hyperglycaemia for baby
oestrogen - made by placenta - increases uteroplacental blood flow, stimulates uterine growth and sensitises the endometrium to oxytocin. increase VTE risk
progesterone - wide variety of roles. uterine relaxation, breast development, vasodilation
what changes are seen to skin and MSK system in pregnancy?
increased melanocyte stimulating hormone (MSH) - hyperpigmentation - linea nigra
increase in weight - fetus, blood volume, placenta etc , breast enlargmnet
MSK - relaxation of ligaments ready for birth, widening of pubic symphysis
describe the development of the placenta.
derived from materal and fetal parts
fetus - oocyte divides and starts to differentiate.
eventually becomes a blastocyst with inner and outer cell mass.
the throphoblasts of fetal part invade the materal part (inner lining of endometium - deducia)
the deducia contains spiral arteries which drain into intervilous spaces
the fetal cells orgnaise to form a villous tree of fetal blood which sits between these spaces - increases S.A and contact between maternal and fetal blood for gas exchange
describe the structure of the placenta
placenta consists of both maternal and fetal material.
the maternal endometrium has been invaded by fetal tissue and cells and organised to give the following..
- The maternal uterine artery supplies spiral arteries within the placenta.
- spiral arteries these drain into the intervillous space - low resistance, low pressure vascular bed.
- the 2 fetal umbilical artery (arise from internal iliac arteries) supply the chorionic villous which descend into the intervillous space and come into close contact with maternal blood
- allows gas exchange, nutrient exchange and other exchange.
what are the functions of the placenta?
- gas exchange - O2 and CO2
- nutrient and waste exchange - glucose, urea etc
- metabolic functions - contains some enzymes for metabolism of drugs
- Endocrine functions - hCG maintains corpus luteum for progesterone in early preg. progesterone secreted later responsible for maternal adaptations to support pregnancy. oestrogens also support fetal growth and prepare endometrium for birth. human placental lactogen - insulin insensitivity for growth
- transfer of immune complexes - igG gives passive immunity to fetus
describe the gas exchange seen across placenta
deoxygenated blood via 2 fetal umbilical arteies (from internal iliac artery) supplies blood to chorionic villous tree
this is is close contact with the intervillous space where blood is supplied from materal spiral artery (oxygenated)
hence diffusion of CO2 and O2 occurs
oxygenated blood leaves fetal chorionic villous tree and enters the umbilical vein to circulate fetal circulation.
describe the layers of the uterine wall
what is the equation for uteroplacental blood flow?
UBF = difference in uterine arterial and venous pressure / uterine vascular resistance
V=IR
what factors influence uterine blood flow?
V= IR
hence
pressure difference - increase in uterine arterial pressure or reduced venous pressure. OR reduced resistance…
increased venous pressure - from contractions, IVC compression and valsalva during labour - can reduce flow
maternal arterial hypotension - e.g. bleeding, aorta compression, sympathetic block can reduce flow
increased vascular resistance e.g. pre-eclampsia, vasoconstrictors - can reduce flow
what is the double bohr effect?
bohr effect describes the right shift of O2 dissciation curve seen with acidosis
across placenta this is seen as a 2 fold effect
as CO2 crosses placenta to maternal circulation, it causes drop in pH and right shift of materanl Hb dissociation curve - mum therefore gives up O2.
as CO2 leaves the fetus - shift fetal Hb to the left - higher affinity for O2
how is fetal blood adapted to take O2 from mum?
fetal Hb subunits have naturally a higher affinity for O2
double bohr effect
increased 2,3 DPG in maternal blood - shifts to right
how does haldane effect play a role in transfer of gases across placenta
as O2 enters fetal circulation and Hb becomes oxygenated, it has less affintiy for CO2 and hence less carbamino Hb produced.
as O2 leaves maternal circulation, deoxygenated Hb has more addintiy for CO2 so more CO2 can be carried as carbamino compounds
= 2 fold
describe the mechanisms of transport across placenta..
simple diffusion - CO2, O2
fasciliated diffusion - glucose, aa
primary active transport - iron, calcium
secondary AT - amino acids
ionic transport - channels
osmosis
pinocytosis - IgG
draw a graph to show how hormones change throughout pregnancy..
hCG - down at 12 weeks.
progesterone - sharp rise and levels out around 15 weeks
oestrogen steady rise from 12 weeks
hpl - steady rise from 5 weeks
what factors affect transport of drugs across placenta?
ficks principle describes the rate of diffusion as being equal to
Kx S.A x Conc difference / distance
K = diffusion contant for a specific drug - depends on molecular weight, ionisation, lipid solubilty, protein binding etc
therefore increasing S.A, conc difference and reducing S.A
inturn
grahams law - diffusion proportional to 1/root MW - hence larger molecules slower diffusion
ionisation - will also slow down diffusion, hence pH and pKA will influence this.
lipid solubility will increase diffusion.
protein binding - the more free portion, the more can diffuse (in pregancy PB is reduced)
on top of this placental blood flow!
describe the significance of transfer of local anaesthetic agents across the placenta…
LA are weak bases
ionise below their pKa
fetal blood is more acidic than materal
unionised LA will cross placenta - small and lipid soluble.
then become ionised at fetal pH
ion trapping can occur
can result in toxic levels in fetus
describe the transfer of common anaesthetic agents across the placenta
volatiles - all cross - small and lipid soluble hence rapid transfer
opioids and benzos - lipid soluble and cross placenta freely.
muscle relaxants - large and charged - do not cross placenta easily.
what are the risks of pethidine in pregnancy?
active metabolite - norpethidine is proconvulsant and causes sedation and resp depression.
longer half life in fetus due to poorer metabolism.
describe the physiology of parturition
divided into 4 phases
phase 1 = quiescence - from conception to initiiation of parturition, the myometrium is inhibited e.g. by progesterone and other hormones
phase 2 = during last 6 weeks of pregnancy, the myometrium is activated by oestrogen. upregulation of oxytocin and prostaglandin receptors
phase 3 - stimulation occurs with onset of labour and contractions start, cervix dilates. all stimulated by oxytocin and prostaglandins. 3 stages of labour occur here.
phase 4 - after birth - control of bleeding and reverting back to pre-pregnant state. the delivery of placenta allows drop in O + P. oxytocin helps with contraction of myometrium to stop bleeding.
what are the 3 stages of labour
First Stage: Cervical dilation and contractions progessively become stronger and more frequent
Second Stage: fully dilated cervix. Delivery of the baby (pushing and descent).
Third Stage: Delivery of the placenta.
how does pregnancy affect drug handling
pharmacokinetic
- absorption - changes to CO may increase gut absorption however slowed gastric emptying
-distribution - changes to protein binding - reduced albumin. also increased plasma volume
- metabolism - reduced plasma cholinesterases
- excretion - increased renal blood flow and GFR
pharmacodynamics
* reduced MAC
what consideration are made for a GA in pregnancy
airway - more likely to be difficult due to engorgement of soft tissues, large breasts. prepare difficult airway trolley, use Mcgrath. RSI after 12 weeks due to aspiration risk from reduced LOS and increased gastric pressures
breathing - smaller FRC so good pre-oxygenation, may need to compromise position with surgeons. could use PEEP. also higher O2 consumption so risk of desat is higher
circulation - aortocaval compression - left lateral tilt- can get reduced preload and loss of CO.
lower MAC
faster onset of inhalation anaesthetic due to lower FRC
what is aortocaval compression and how should it be managed?
from 20 weeks the size of gravid uterus can compress aorta and vena cava when mum is supine
reduces venous return and CO
reduces renal and uterine blood flow and hence can cause fetal distress
lie left lateral tilt 15 degrees to reduce this.
do you know any abnormalities of placental development?
pre-eclampsia - thought to develop from abnromal placentation whereby there is high resistance in the placental bed leading to HTN, proteinuria and organ dysfunction (e.g. liver, thrombocytopenia, renal)
placenta increta - chorionic tissue of fetus pentrates the myometrium (usually just endometrium)
placenta percreta - invades even further into surroudning structures.
what is HELLP
haemolysis, elevated liver enzymes, low platelets
complication of pre-eclampsia
symptoms of pre-eclampsia
blurred vision, headaches
proteinuria
oedema/ swelling
can lead to eclampsia (seizures)
what are uterotonics?
drugs that increase uterine tone
given to induce labour and prevent PPH
e.g. oxytocin, ergometrine, carboprost and misoprostol
when is oxytocin used?
prophylactically to all women in 3rd stage of labour to reduce PPH
how is pre-term labour defined?
regular uterine contractions with cervical dilation from between 20 to 37 weeks.
what are tocolytic agents
drugs that relax the uterus and inhibit uterine contractions.
used for preventing pre-term labour or fetal distress in event of uterine inversion.
e.g. volatiles, nitrates, CaCB (nifedipine), oxtocin receptor antagonists (Atosiban)
how does the oxytocin receptor work?
GPCR Gq
increases IP3 and DAG
results in increased calcium in smooth muscle
acts via calmodulin to cause muscle contractions.
what is oxytocin
endogenous peptide hormone (9aa) secreted from posterior pituitary in response to hypothalamic stimulation.
its binds Oxytocin receptor (GPCR Gq) and results in uterine contractions
naturally this increases uterine contractions in labour.
also synthetically produced and given as a drug - syntocin - can augment labour and treat PPH
what is syntocin ?
synthetic oxytocin used in maternity to treat PPH & induce labour - 1st line uterotonic
comes as clear colourless solution - 1ml vials of 5 - 10 units. kept in the fridge
can be given as IM dose or slow IV infusion.
usually give 5 units to start with but can go up to 10 units / hour for 4 hours if needed.
pharmacodynamics
- GPCR Gq - contraction
- vasodilation - flushing and hypotension
- headaches
- can cause water retention and Na retension (similar to ADH)
- N&V
pharmacokinetics
* absorbed either IV or IM , can cross placenta
* 30% PB
* metabolised by liver and plasma oxytocinases
* excretion - bile and renal
* half life 1-6 mins
what is ergometrine?
second line uterotonic drug
used for PPH or treatment of miscariage/ abortion
comes in tablet and solution form
also combined with syntocin - syntometrine
IV at 125ug and IM up to 500ug
unclear MoA
causes uterine contractions
coronary vasospasm and HTN - should be avoided in pre-eclampsia / HTN
CNS - headaches, tinnitus
N&V ++
what is carboprost?
synthetic analogue of prostaglandin F2a
used as 3rd line uterotonic for PPH
given as IM injection of 250ug up to 2mg
acts on PG receptors in myometrium to cause muscle contraction.
side effects include - hypertension, flushing, BRONCHOSPASM, N&V
caution in asthma, IHD
how is PPH managed pharamocologically
1st line -oxytocin
2nd line - ergometrine
3rd line IM carboprost
avoid ergometrine in HTN
avoid carboprost in asthma
what is misoprostol?
prostaglandin E2 analogue
used as adjunct in PPH
can be given orally, rectally, pessary
can also be used to induce labour and medical management of miscarriage
can cause flushing, headaches, diarrhoea
what is first line as a tocolytic agent.. tell me about this drug?
nifidipine - Ca CB
inhibits uterine muscle contraction in preterm labour though blocking L type Ca channels and reducing intracellular Ca.
given orally and takes 15-20mins to work
side effects
- hypotension , reflex tachy and increased CO
- headaches
- constipation
what is atosiban
oxytocin receptor antogonist
2nd line tocolytic agent
used for pre-term labour
given as IV injection / infusion
how is indomethacin used as a tocolytic agent?
COX inhibitor
inhibits production of prostaglandins
prostaglandins normally involved in uterine contractions and labour
hence inhibits this
what do volatile agents do to uterine tone?
relax uterine contraction - dose dependant manner
sevo,des and halothalne the most
isoflurane - less so
also cause uterine vasodilation and increase risk of haemorhage
this is important when considering GA for C section - increase risk of bleeding.
when may nitrates be needed in maternity
emergency tocolysis IV GTN
what defines a major obstertic haemorrhage?
more than 1500ml
what define PPH?
blood loss of 500ml vaginally post delivery
or 1L with C section
may be primary within first 24 hr
or secondary after 24 hr to 12 weeks
what are the causes of obstertic haemorrhage?
antepartum - placental praevia, uterine rupture, trauma , abruption
post partum - tone , tissue, thrombin, trauma
what are the risk factors for a PPH?
tone - previous PPH, larger uterus (multiple pregancies, tiwns, macrosomia). general anaesthesia, prolonged labour , tocolytic drugs
tissue - retained placenta
thrombin - sepsis, DIC, coagulopathy , pre-eclampsia
trauma - instrumental delivery, C section
what is uterine rupture associated with?
previous C section
induction of labour
whats the Hb, fibrinogen, platelet target for obstetric haemorrhage?
platelets >100 x10^9 / l
Hb >80g/L
fibrinogen > 2 g/l
in what forms can fibrinogen be given?
FFP
cryoprecipitate
fibrinogen concentrate
what drugs may help with PPH
syntocin - 5-10units or as infusion 10unit/hr. can cause hypotension
ergometrine - 500ug IV or IM
can cause hypertension and bronchospasm
carboprost - 3rd line 250ug IM
bronchospasm, contraindicated in asthma
misoprostol - 3rd line - given PR
common causes of cardiac arrest in pregnancy
P.E
haemorrhage
sepsis
others - amniotic fluid embolus
