T2 L18 Physiology of Pregnancy Flashcards
What happens to the physiological demand of the foetus (and placenta) during pregnancy?
Physiological demand increases:
- 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)
By what % does the maternal plasma volume increase in pregnancy?
40%
2.5 L to 3.7 L by end of pregnancy
How much weight does the mother gain during pregnancy?
11-13 kg weight gain (8-10kg fluid)
What happens to the plasma colloid osmotic (oncotic) pressure? What does this lead to?
Plasma colloid osmotic (oncotic) pressure falls
This causes:
- A shift of fluid into extra cellular space
- Increased hydration of connective tissue
- Oedema (lower limbs, hands and face)
COMPLETE THE SENTENCE
_________ has a +ve effect on angiotensinogen
OESTROGEN
COMPLETE THE SENTENCE
_________ has a +ve effect on aldosterone
PROGESTERONE
What is the overall effect of oestrogen and progesterone on the RAAS system?
It increases activity of the RAAS
Describe the RAAS system?
angiotensinogen =>(via RENIN) angiotensin I => (via ACE) angiotensin II => aldosterone => increased Na+ and H2O reabsorption
What is the mechanism of increased plasma volume?
Slight decrease atrial natriuretic peptide (ANP)
Decreased thirst threshold (increased fluid intake)
Re-setting osmostat
INCREASED PLASMA VOLUME
What happens to the haemoglobin concentration during pregnancy?
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
This is called dilutional anaemia
What ion is required for increased cell mass?
Iron
What happens to iron absorption in pregnancy?
(occurs in the gut)
It is increased
What happens to the ferritin levels in pregnancy?
It falls
Is iron supplement required during pregnancy?
No
EXCEPT when pregnant with twins
What happens to blood flow to the uterus during pregnancy?
Uterine artery blood flow increases 3.5 fold
From 95 to 342 ml/min
What happens to the haemostasis during pregnancy?
HYPERCOAGULABLE STATE
-Increase plasma fibrinogen (increased ESR), platelets, factor VIII & von willebrand factor
Why is this hypercoagulable state important during parturition?
500 ml/min blood loss at placental separation
Myometrial contraction - 10% of all fibrinogen used up to prevent further bleeding
So its important that there is enough fibrinogen for this to happen
NOTE: There is an evolutionary balance between thrombosis and haemorrhage
Does the WBC concentration increase or fall during pregnancy?
It increases
There is an increase in neutrophils (reduced apoptosis) and a marked increased around delivery
What does increased blood volume have implications on?
- cardiac output
- peripheral resistance
- blood pressure
What does increased stroke volume require?
Increased SV requires increased heart volume
What changes occurs in the heart during pregnancy?
Heart enlarges by 12% (increased venous return)
What type of murmurs are common in pregnancy?
Innocent systolic murmurs are common (~90%)
What % of innocent murmurs are diastolic murmurs?
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
Why does peripheral resistance decrease in pregnancy?
Progesterone causes peripheral dilation
By what % does peripheral resistance decrease?
35%
COMPLETE THE SENTECE
Week ____ to week ____ shows the greatest decrease in peripheral resistance
Week 0
Week 8
How is the decreased resistance compensated for?
Cardiac output increases
Small change in BP
What physiological changes occurs in the respiratory system during pregnancy?
Increased pulmonary blood flow matched by -
- Increased tidal flow
- Decreased maternal pCO2 & increase maternal pO2
- Increased availability of O2 to tissues and aids passive diffusion at the placenta i.e. higher concentration gradient
What are the effects of cardiovascular & respiratory changes?
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)
What physiological changes occurs in the renal system during pregnancy?
Kidney increases 1cm in size during normal pregnancy
GFR and effective renal plasma flow increase 50+%
BUT tubular reabsorption capacity is unchanged. This leads to a decrease in glucose reabsorption thus glycosuria is common
COMPLETE THE SENTENCE
Plasma levels of creatinine and urea ___________ in pregnancy
DECREASE
Does GFR reduce or increase during the third trimester? By what %?
Decreases
By 15%
Why does urinary tract infections increase during pregnancy?
Because of dilatation of renal pelvis and ureters
This is due to the effect of progesterone
By what % does gastrointestinal reflux increase?
70%
Why is there an increase in gastrointestinal reflux?
Increases due to:
- increase abdominal pressure
- reduced pyloric sphincter with back wash of bile secondary to hormonal changes
How can gastrointestinal reflux be avoided?
- Avoidance of fat and alcohol
- Upright posture and antacids
What happens to gut motility during pregnancy? What does this lead to?
Slowing of gut motility which leads to constipation
NOTE: This is due to the effect of progesterone
What happens to glucose metabolism in the 1st trimester?
Increased sensitivity to insulin
THUS
mothers increase glycogen synthesis and fat deposition
What happens to glucose metabolism in the 2nd trimester?
INSULIN RESISTANCE
-cortisol, progesterone, HPL, & 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)
Why is folate important?
DNA synthesis, repair and regulation
-important in rapid cell division (embryos)
-deficiency in pregnancy associated with neural tube
defects (NTDs)
RBC development
-deficiency lead to macrocytic anaemia
What is the daily requirement for folate?
Daily requirement increased from 50mg to 400mg (normal diet)
COMPLETE THE SENTENCE
Plasma folate represents ___________________
Current nutritional status
What mechanism do humans have to compensate for dietary deficiency of folate?
Significant tissue stores (e.g. liver)
Dietary deficiency can take months to become significant
Name a good biomarker for folate levels
RBC folate
Is a folate supplement needed during pregnancy?
No
BUT
folate prevents neural tube defects so its routinely given from preconception to 3 months
What happens to thyroid function during pregnancy?
In general thyroid function remains unchanged
- 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
NOTE: If hypothyroid may need to increase dose due to increased TBG levels
Is the placenta an endocrine organ?
YES
Which protein hormones are secreted by the placenta?
- hCG (human chorionic gonadotrophin)
- hPL (human placental lactogen)
- hPG (human placental gonadotrophin
- CRH (corticotropin releasing hormone)
Which steroid hormones are secreted by the placenta?
- Progesterone
- Oestrogen (oestriol)
When is hCG first detectable?
8-9 days after ovulation & peaks at 8-10 weeks of pregnancy
Which subunit of hCG is used in pregnancy tests?
Beta
What happens to the hCG levels every 48-72 hours?
It doubles
Where is hCG produced?
In the trophoblast
When is hCG produced in large quantities?
Produced in large quantities by hydatidiform molar pregnancy & choriocarcinoma
When is hCG significantly lower?
Ectopic pregnancy & risk of miscarriages
The alpha-hCG is very similar to which hormones?
LH
FSH
TSH
It has LH type properties but longer half life
What is the half life of alpha-hCG?
24 hours
What is the role of the alpha-hCG?
- 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
The human placental lactogen (hPL) is very similar to which hormones?
Prolactin
Growth Hormone
What is the relationship between the hPL levels and the placenta size?
The bigger the placenta, the more hPL
What is the half life of hPL?
30 minutes
What does hPL not function as?
Not functioning as a stimulator of lactogenesis
What is the role of the hPL?
Alters maternal carbohydrate and lipid metabolism to provide for foetal requirements:
- mobilizes 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
What is the role of the placental growth hormone (hPG)?
- Responsible for regulating fetal growth
- Induces maternal insulin resistance
NOTE: No evidence of that maternal GH or fetal GH required for fetal growth
What is the effect of placental corticotrophin-releasing hormone (CRH)?
Stimulates production of maternal:
- adrenocorticotropin hormone (ACTH)
- cortisol
Why is increased level of 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
What can increased cortisol lead to in the mother?
Increased maternal glucose levels
What is the role of progesterone?
Maintains uterine quiescence (inactivity or dormancy) by decreasing uterine electrical activity
Immune suppressor ( HLA )
Lobulo-alveolar development in breasts
Substrate for fetal adrenal corticoid synthesis eg cortisol
What is the role of 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)
Which hormone is converted to oestriol?
Both maternal & foetal dehydroepiandrosterone (DHEA-S) via the enzyme aromatase
What is makes us 90% of the oestrogen? REMEBER oestrogen is a group of hormones
Oestriol
What is the effect of oestriol?
Modulates uteroplacental blood flow
