Developmental - Maternal physiology during pregnancy Flashcards
What is beta HCG, where is it secreted from? and when can it be detected in the maternal circulation versus maternal urine.
beta human chorionic gonadotropin is a glycoprotein hormone with structure similar to that of LH, FSH, TSH.
secreted from the placenta
Detectable in maternal circulation: 10 days
Detectable in maternal urine: 10 days
Describe the rise of hcg during pregnancy. How fast is the rise and when is the peak reached
Rapid rise
Doubles every 2 days until peak is reached after 10 weeks gestation
Describe the endocrine process that prevents miscarriage in early pregnancy
- In the 2nd half of the menstrual cycle, the corpus luteum secretes progesterone and a small amount of oestrogen.
- after 14 days and without implantation, corpus luteum degenerates into corpus albicans
- If embryo implants in uterus or fallopian tube (ectopic) then syncytiotrophoblast cells of the newly formed placenta produce beta hcg which stimulates the corpus luteum to keep secreting progesterone. This prevents sloughing of the placenta which would cause miscarriage
What are the functions of the hormone beta hcg
- Prevent degeneration of the corpus luteum after implantation of a zygote
- To suppress the maternal immune response, protecting the placenta and embryo from immune destruction.
What happens to beta hcg concentration at 10 weeks? Why does this occur
Peak beta hcg levels are reached. At this point the placenta takes over progesterone synthesis and secretion from the corpus luteum. The beta hcg level then falls and the corpus luteum degenerates
What is Human Placental Lactogen (hPL). Where is it secreted from
Polypeptide hormone similar to GH
Secretion: syncytiotrophoblast cells of placenta
Describe the rise of human Placental Lactogen (hPL) levels during pregnancy
hPL levels increase through pregnancy in proportion to fetal and placental growth, peaking near term
What are the functions of human Placental Lactogen
Ensure provision of nutrients for the growing fetus through manipulation of maternal metabolism.
- Increased maternal lipolysis (ffas availability)
- Decreased maternal insulin sensitivity (glucose avail)
- Stimulation of breast growth and development
What type of hormone is progesterone
A steroid hormone
How is progesterone secreted during pregnancy
Corpus Luteum up to 10 weeks (thanks to beta hcg)
Then placenta takes over in second and third trimester
What are the main functions of progesterone
The ‘pregnancy hormone’
- Prepare endometrium for implantation
- Promote endometrial growth following implantation
- Uterine muscle relaxation (prevent miscarriage)
- Formation of cervical mucus plug (protect developing fetus from ascending infection)
- Development of milk glands in preparation for lactation
Also responsible for many other physiological changes during pregnancy
Name the three types of oestrogen synthesized by the placenta. How is the synthesis of these types determined and which is the important type during pregnancy
Oestradiol
Oestrone
Oestriol
Each are made from different precursors
The amount of precursors for each available determines the synthesis of each type.
Oestriol is produced from a fetal adrenal precursor called dehydroepiandrostenedione sulphate. Hence oestriol production is under the control of the growing fetus
What controls uteroplacental blood flow during pregnancy. How is this control achieved
The fetus.
The fetal adrenals produce the precursor dehydroepiandrostenedione sulphate which are delivered to the placenta and favour the synthesis and secretion of oestriol (over oestrone and oestradiol).
Oestriol Increases uteroplacental blood flow.
(oestradiol is the oestrogen that regulates the menstrual cycle)
What are the roles of oestrogens during pregnancy
- To increase uteroplacental blood flow
- Stimulate uterine growth
- Sensitise myometrium to oxytocin (reduce PPH)
- Procoagulant (reduce PPH, VTE risk)
Describe the changes to thyroid hormones during pregnancy
Oestriol –> liver: synthesis of more thyroxine-binding globulin –> decrease unbound T3 and T4 –> sensed by hypothalamus –> increase TRH –> increase TSH –> T3 and T4 back to normal
What is Sheehan’s syndrome
Oestrogen –> dramatic increase PRL during pregnancy to prep the breasts for lacatation –> pituitary gland doubles in size with much higher metabolic demands: vulnerable to ischaemia. If effective circulating volume diminished during PPH –> ischaemia/infarction of the pituitary gland.
Which hormone causes increased secretion of prolactin during pregnancy and doubling in size of the pituitary gland as a result
Oestrogen
Discuss maternal calcium regulation during pregnancy
Fetal demand Ca is high. Ca+ moved from maternal into fetal circulation across placenta –> reduced maternal ionized calcium –> Increased maternal PTH –> increased renal reabsorption Ca, activation of vit D and resorption of bone.
In combination with LMWH –> osteopaenia of bone
When do the respiratory changes in pregnancy become significant
> 20 weeks
How is the airway affected during pregnancy
- Capillary engorgement (oestrogen) –> oedema and swelling of oropharyngeal and laryngeal mucosa
- Weight gain
——> larger breasts
——> short neck - Increased mucosal vascularity and bleeding (worsened by low plt in PET)
How is the minute ventilation affected in pregnancy
At term: Ve increase by 50%
- Vt increases 40%
- RR increases 10%
How does pregnancy affect minute ventilation
Progesterone:
- VT increased by 40% at term
- RR increased 10% at term
- Ve increased 50% at term and even further during la our due to pain
How is anatomical dead space affected by pregnancy
Progesterone
Causes bronchodilation—> increased (minimally) anatomical dead space
Progesterone induced smooth muscle relaxation
What is the normal PaCO2 and HCO3 in pregnancy and why.
PaCO2 —> 4.3
HCO3- —> 20
Fetus: increased CO2 production
Mother: increased Ve
Overall: PaCO2 down
Kidneys respond to respiratory alkalosis by excreting more HCO3-
Why is it important to maintain normocapnoea of 4.3 (rather than 5.0) when ventilating a pregnant mom?
Avoid maternal acidosis
- the fetus cannot correct a pH disturbance by respiratory or renal compensation. Therefore maternal respiratory acidosis can cause fetal acidosis
Avoid maternal alkalosis
- alkalosis will shift the maternal P50 of the OHDC to the left, reducing O2 transfer to the fetus with the potential for feral hypoxia.
What is the affect of pregnancy on lung volumes
Upward displacement of the diaphragm. No restriction of diaphragmatic contraction.
- Reduced FRC 20% upright
- Reduced FRC 30% supine
[mainly due to reduction in RV]
How is vital capacity affected by pregnancy?
It’s not
How is oxygen consumption affected by pregnancy
20% increase at term.
How is respiratory compliance affected by pregnancy
Lung compliance: unaffected
Thoracic wall compliance reduced by 20% —> from upward displacement of diaphragm.
How is thoracic wall compliance affected by pregnancy
Upward displacement of the diaphragm leads to 20% reduction in thoracic wall compliance
At what gestation does the risk of GORD increase?
At what gestation is RSII indicated
Reflux risk increases at 12 weeks
RSI is indicated at 16 weeks. (UpToDate says 18-20weeks)
What is the risk of failed intubation in obstetric patients compared to the general population
10 times greater risk of failed intubation (chambers says 8 x)
General population: 1 in 3000
Obstetric population: 1 in 300
Why do obstetric patients desaturate quickly
Combination of reduced FRC (30%) and increased oxygen consumption (20%)
What is the leading indirect cause of death in pregnant patients?
Cardiac disease
How does pregnancy affect the maternal blood volume? Describe the constituents of this change and how this changes occur
Increases by 20 - 30 %
- Red cell mass by 20-30%
(Increased EPO secreted in response to: increase GFR and increased nephron metabolic requirement - paracrine and auto crime mechanisms) - Plasma volume increases 45%
- oestrogen stimulates RAAS. - Due to above Hb 15 —> 12 and Hct 40 —> 35
= Physiological anaemia
Why do pregnant patients need haematinic
Increased GFR and metabolic demand on the kidney recruits paracrine and auto crime mechanisms to increase renal secretion of EPO.
Increased EPO leads to increased haemopoeisis which requires additional haematinics: iron, folate, B12 as stores are usually insufficient to meet this additional requirement.
How much blood is squeezed into systemic circulation during each uterine contraction in labour.
300 - 500 mls
How much blood is autotransfused in the post partum period during uterine involution
500 mls
Describe how pregnancy affects Cardiac Output and how this effect is achieved
Increased by 50% by the 3rd trimester
- Afterload reduced
- SVR down by 20% (Progesterone VD) - HR increased by 25%
- Reflex to decrease SVR and hence BP - Increased preload –> SV increases by 30%
- occurs during the 1st trimester - Myocardial contractility is unchanged
In summary 1. SVR down 20% 2. HR up 25% 3. Preolad --> SV up 30% 4. No change to myocardial contractility Overall: CO up 50% by 3rd trimester
How is cardiac output affected during labour
Increased by a further 25 - 50% due to response to catecholamines
How does CO change during uterine contractions
Increases by 20 - 30%
How is cardiac output affected in the post partum period
following delivery, uterine involution results in an autotransfusion of ± 500 ml of blood and an increase in cardiac output 60 - 80%
High risk period for parturients at risk of cardiac failure
At what gestation does aortocaval compression become relevant
20 weeks
What are the haemodynamic implications of aortocaval compression
- Reduced maternal venous return –> reduced preload –> reduced CO –> nausea/pallor/hypotension/CVS collapse when supine resolved when lateral
- Reduced placental blood flow
- No autoregulation
- Flow directly proportional to perfusion pressure
- Reduced VR –> reduced preload –> reduced CO –> reduced placental flow
- Aorta compression also reduces uteroplacental flow impairing fetal gas exchange
How does the the non-anaesthetized parturient compensate for aorto-caval compression
SNS
- -> increase HR and SVR
- -> Blood bypass compressed IVC viacollateral pathways
1. Azygos veins
2. Paravertebral veins
3. Epidural veins
What is the mechanism for increased risk of GORD in pregnant patients?
- LOS tone low (Progesterone)
- Mechanical changes at gastro-oesophageal junction (gravid uterus)
- Increased intra-gastric pressure (gravid Ux 3rd TM)
- Gastric pH: gastrin secreted by placenta at 15th week –> increased gastric volume and decreased pH.
During labour
5. Delayed gastric emptying due to SNS. Plus opioids
What is Mendelson’s syndrome
Pneumonitis resulting from pulmonary aspiration of acidic gastric contents under general anaesthesia.
Aspiration of > 25 mL at pH < 2.5 –> severe pneumonitis
What is the normal White Cell count in pregnancy
WCC: 6 –> 16 (may increase to 30 in labour)
x 1000 mm^3
How does the platelet count change during pregnancy
Platelet count lower limit of normal at term is 115 (x 10^9/L)
- haemodilution
- shorter platelet lifespan
How does a normal FBC look like in pregnancy compared to non-pregnant female
Non-Pregnant Hb 15 Hct: 40% WCC 4 - 10 Plt 150 - 450
Pregnant Hb 12 Hct 35% WCC 6 - 16 (can increase to 30 during labour) Plt 115 - 450
Why are pregnant patients more likely to develop VTE
VIRCHOW’S TRIAD
STASIS
- Increased venous capacitance (Prog/oestrogen)
- Compression large veins gravid Ux
HYPERCOAGULABILITY
- Increased fibrinogen
- Increased clotting factors 2, 7, 8, 9, 10, 12
- Reduced protein S
- Resistance to activated protein C
- Reduced fibrinolysis
ENDOTHELIAL DAMAGE
1. During delivery
What anatomical changes occur to the urogenital system in pregnancy
Progesterone
- Smooth muscle relaxation –> dilatation renal pelvices and ureters
Gravid uterus
- Increased likelihood of mechanical obstruction
Increased risk of urinary tract infection
How does pregnancy affect GFR
RBF increases 50% reflecting the increased CO in pregnancy. GFR is increased by a similar amount
Pregnant patients therefore have lower serum urea and creatinine concentrations
How is uric acid affected in pregnancy
First trimester, uric acid decreases due to increased GFR
By the 3rd trimester uric acid increases above the pre-pregnancy level.
Severity of hyperuricaemia has been contraversially linked to severity of pre-eclampsia.
Why is glycosuria an unreliable screening tool for diabetes in pregnancy?
Increased GFR exceeds Tmax and tubules cannot achieve 100% glucose absorption. Hence, glycosuria is common in pregnancy and dipstix is not a reliable test for diabetes in pregnancy
Is proteinuria normal in pregnancy
Tubular protein reabsorption is insufficient to match the 50% increase in the GFR.
Pre-pregnancy upper limit of normal for proteinuria is 150 mg in 24 hours
Pregnancy upper limit of normal for proteinuria is 300 mg in 24 hours.
Pre-eclampsia causes a pathological increase in proteinuria.
How is the MAC of volatile anaesthetic agents affected by pregnancy? What are the mechanisms for this change?
Reduces the MAC by 30 - 40%
Mechanisms:
1. Progesterone (sedative effects)
- Beta -endorphins
- Placenta secretes beta-endorphins throughout pregnancy and especially in labour
- Thought to reduce MAC and increase sensitivity to local anaesthetics (1.8 ml spinal dose)
How is epidural pressure influenced by pregnancy? Describe the mechanism for this change.
Pre-pregnancy: -1 cmH2O
Pregnancy: + 1 cmH2O
1st stage of labour: 4 - 10 cmH2O
Second stage labour during bearing down: 60 cmH2O
Mechanism:
- Engorgement of epidural veins secondary to mechanical compression of IVC by the gravid uterus.
How is CSF pressure changed by pregnancy
Pre-pregnancy: 18 cmH2O
Pregnancy: 18 cmH2O
Second stage labour: up to 70 cmH2O
How does pregnancy affect duration of action of succinylcholine and why?
Increased plasma volume –> liver cannot keep up
Diluted plasma proteins
- Plasma cholinesterase decrease by 25%
- Albumin decrease by 30%
As plasma cholinesterase is reduced, theoretically succinylcholine duration of action should be prolonged. But it isn’t.
How is hepatic physiology affected by pregnancy
Mild deranged LFTS:
- Elevated: ALT, LDH, GGT, ALP
Hepatic protein production does not keep pace with increased plasma volumes –> dilution
(except clotting factors)
How does pregnancy affect the musculoskeletal system. Describe the mechanism
Ligaments become increasingly lax as pregnancy progresses.
This is due to placental secretion of the hormone: relaxin.
