18. Physiology of pregnancy Flashcards
How does the foetus (and the placenta) affect physiological demands?
An increase in physiological demands for the foetus (& placenta):
- Nutrients (e.g. O2, amino acids, glucose)
- amniotic fluid production
- Removal of foetal waste products (e.g. CO2, nitrogen compounds)
Requires increased:
- Nutrient content (Gastro intestinal)
- Oxygen content (Pulmonary & cardiovascular)
List the changes that occur as a result of pregnancy
Plasma volume changes Cardiovascular changes Respiratory changes Renal changes Gastro-intestinal Endocrine changes
Effect of pregnancy on volume homeostasis?
A rapid increase in plasma volume by 40%
2.5 L to 3.7 L by end of pregnancy
11-13 kg weight gain (8-10kg fluid)
Plasma colloid osmotic (oncotic) pressure falls
What is the effect of decreased plasma colloid osmotic (oncotic) pressure in pregnancy?
Plasma colloid osmotic (oncotic) pressure falls
Causes a shift of fluid into extra cellular space
Increased hydration of connective tissue
Oedema (lower limbs, hands and face)
What is the mechanism of increased plasma volume in pregnancy?
Oestrogen positive feedback effect on angiotensinogen
Progesterone positive feedback effect on aldosterone
resulting in more RAAS system and aldosterone and consequently more Na+ and water reabsorption at the kidney.
There is also:
- a slight decrease in ANP
- decreased thirst threshold (so more fluid intake)
- resetting osmostat
this results in increased plasma volume
Red blood cells and oxygen availability in pregnancy
Haemoglobin;
red cell mass increased by 25% (1.3L to 1.7L)
plasma volume increased by 40%
13.3 to 10.9 g/dL at 36 weeks
dilutional anaemia
Iron is required for the increased red cell mass
fall in ferritin levels
increased iron absorption from gut
No need for routine Fe supplementation except for twins
Delivery of blood to the uterus; uterine artery blood flow increases 3.5 fold from 95 to 342 ml/min
Haemostasis in pregnancy
Hypercoagulable state:
- Increase plasma fibrinogen (increased ESR (erythrocyte sedimentation rate))
- increased platelets
- increased factor VIII & von willebrand factor
Marked effect at delivery:
- 500 ml/min blood loss at placental separation
- myometrial contraction - 10% of all fibrinogen used up
Evolutionary balance between thrombosis and haemorrhage
White blood cells in pregnancy
Concentration does not fall during pregnancy
Total WBC increases in pregnancy
Increase in neutrophils (reduced apoptosis)
Marked increased around delivery
What are the implications of the increased blood volume during pregnancy
Increased blood volume has implications on:
- cardiac output (SV x HR)
- peripheral resistance
- blood pressure
Heart changes during pregnancy
Increased cardiac output needs increased stroke volume
increased stroke volume needs increased heart volume
Heart enlarges by 12% (increased venous return)
Innocent systolic murmurs are common (~90%)
Diastolic murmurs (~20%) – require investigation to rule out other pathologies,
- may be innocent – reflecting increased flow across atrioventricular valves
- will require further investigation to rule out cardiopathies – but be aware…
- change in cardiac axis/position result in changes on ECG and xray
Also… Uterus pushing up against the diaphragm can cause the maternal heart to shift up in the chest cavity
Peripheral resistance during pregnancy
Peripheral vasodilatation (effect of progesterone) Peripheral resistance decreases by 35%
Blood pressure during pregnancy
Decrease in resistance is partly compensated by increase in cardiac output
Results in a small change in blood pressure
Systolic dips slightly then increases again
Diastolic dips by about 20mmHg from around week 8 then starts to increase again at around week 16 back to normal at around week 38
Respiratory system in pregnancy
Increased pulmonary blood flow matched by -
Increase tidal flow
Decrease maternal pCO2 & increase maternal pO2
->
Increased availability of O2 to tissues and aids passive diffusion at the placenta i.e. higher concentration gradient
What is the effect of cardiovascular and respiratory changes in pregnancy?
High blood flow maximises pO2 on maternal side of the placenta
Foetal haemoglobin (HbF) has a higher affinity for O2 compared with maternal adult Hb (HbA)
Increased cardiac output may increase flow in skin aiding heat loss (high metabolic state)
The effect of pregnancy on the renal system
Kidney increases 1cm in size during normal pregnancy
GFR and effective renal plasma flow increase 50+%
BUT tubular reabsorption capacity is unchanged
leads to a decrease in glucose reabsorption thus glycosuria (glucose excretion in urine) is common
Plasma levels of creatinine and urea decrease in pregnancy
All the increments are present by the second trimester
Reduction in GFR of 15 % during the third trimester
Dilatation of renal pelvis and ureters (progesterone) - increased urinary tract infections in pregnancy
Effect of pregnancy on gastrointestinal system
Gastro-oesophageal reflux up to 70 %
due to increase abdominal pressure, reduced pyloric sphincter with back wash of bile secondary to hormonal changes
simple measures: avoidance of fat and alcohol
upright posture and antacids
Slowing of gut motility and constipation (progesterone effect)
Glucose metabolism in pregnancy
First trimester: increased sensitivity to insulin thus mothers increase glycogen synthesis and fat deposition
Second trimester: insulin resistance
cortisol, progesterone, HPL (human placental lactogen), & oestrogen are all insulin antagonists
thus glucose levels may rise and there is an increase in fatty acids (another source of energy for the fetus)
Folate in pregnancy
Needed for DNA synthesis, repair and regulation
- Important in rapid cell division (embryos)
- Deficiency in pregnancy associated with neural tube defects (NTDs)
Needed for RBC development
- deficiency can lead to macrocytic anaemia
Daily requirement increased from 50mg to 400mg (normal diet)
Plasma folate represents current nutritional status, but
Significant tissue stores (e.g. liver) – RBC folate is a good biomarker (no change in pregnancy)
- Dietary deficiency can take months to become significant
No need for folate supplementation but prevents neural tube defects thus routinely given preconception to 3 months
Thyroid function during pregnancy
Increased iodine absorption
Increased serum T3 and T4 levels
Increase in thyroid binding globulin (oestrogen)
As only unbound T3 and T4 is active, levels of free T3 and T4 remain the same or fall slightly
In general thyroid function remains unchanged
If hypothyroid may need to increase dose due to increased TBG levels
What hormones does the placenta, as an endocrine organ, secrete?
Protein hormones:
- hCG (human chorionic gonadotrophin)
- hPL (human placental lactogen)
- hPG (human placental gonadotrophin
- CRH (corticotropin releasing hormone)
Steroids:
- Progesterone
- Oestrogen (oestriol)
Human chorionic gonadotrophin (hCG)
First detectable 8-9 days after ovulation & peaks at 8-10 weeks
Beta subunit used as the pregnancy test
Doubles every 48-72 hours
Produced by the trophoblast
Alpha subunit very similar to LH, FSH,TSH
Has LH type properties but longer half life (24 h)
Maintains corpus luteum secretion of progesterone & oestrogen
Decreases as the placental production of progesterone increases
Later in pregnancy may have a role in maternal oestrogen secretion and modulation of the maternal immune response
When is hCG low and when is it high?
Produced in large quantities by hydatidiform molar pregnancy & choriocarcinoma
Usually significantly lower in ectopic pregnancy & risk of miscarriages
Decreases as the placental production of progesterone increases
Later in pregnancy may have a role in maternal oestrogen secretion and modulation of the maternal immune response
Human placental lactogen (hPL)
Similar structure to prolactin and growth hormone
The bigger the placenta, the more hPL
Half life ~ 30 min
Not functioning as a stimulator of lactogenesis
Alters maternal carbohydrate and lipid metabolism to provide for foetal requirements:
- Mobilizing maternal free fatty acids
- Inhibits maternal peripheral uptake of glucose
- Increases insulin release from pancreas
Aim is a steady state of glucose for the fetus
Placental growth hormone (hPG)
Placental Growth Hormone secreted by the placenta responsible for regulating fetal growth
Induces maternal insulin resistance
No evidence of that maternal GH or fetal GH required for fetal growth
Placental corticotrophin-releasing hormone (CRH)
Stimulates production of maternal:
- adrenocorticotropin hormone (ACTH)
- cortisol
? Increased cortisol believed to be detrimental to the foetus ?
- High levels early linked to slower rate of cognitive development post-partum
- High levels late linked to accelerated cognitive development post-partum
Increased cortisol can result in increased maternal glucose
Progesterone
Maintains uterine quiescence by decreasing uterine electrical activity
Immune suppressor ( HLA )
Lobulo-alveolar development in breasts
Substrate for fetal adrenal corticoid synthesis eg cortisol
Oestrogen
Growth of the uterus, cervical changes
Development of ductal system of breasts
Stimulation of prolactin synthesis
Stimulation of corticol binding globulin (CBG), sex hormone binding globulin (SHBG), thyroxin binding globulin (TBG)
Both maternal & foetal dehydroepiandrosterone (DHEA-S) is converted to oestriol (aromatase)
90% as oestriol (to modulating uteroplacental blood flow)
