T2 L18: Physiology of Pregnancy

Question 1

what happens to the plasma volume in pregnancy

Answer 1

increases by 40%
from 2.5-3.7L
11-13kg weight gain

Question 2

what does the decrease in osmotic pressure cause

Answer 2

Causes a shift of fluid into extra cellular space

Increased hydration of connective tissue

Oedema (lower limbs, hands and face)

Question 3

what is the mechanism of increased plasma volume

Answer 3

Slight decrease atrial natriuretic peptide (ANP)

Decreased thirst threshold (increased fluid intake)

Re-setting osmostat

INCREASED PLASMA VOLUME

Question 4

what happens to the red blood cell oxygen availability

Answer 4

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

Question 5

what occurs to iron levels

Answer 5

fall in ferritin levels

increased iron absorption from gut

Question 6

what is a hypercoagulable state and what is its purpose during pregnancy

Answer 6

Increase plasma fibrinogen (increased ESR), platelets, 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

Question 7

what occurs to white blood cells during pregnancy

Answer 7

Concentration does not fall during pregnancy

Total WBC increases in pregnancy

Increase in neutrophils (reduced apoptosis)

Marked increased around delivery

Question 8

what does increased blood volume have implications on in the cardiovascular system

Answer 8

cardiac output

peripheral resistance

blood pressure

Question 9

what is cardiac output and what does SV require to increase

Answer 9

SV x HR

Increased SV requires increased heart volume

Question 10

how does the heart change during pregnancy

Answer 10

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

Question 11

what happens to peripheral resistance

Answer 11

Peripheral vasodilatation (effect of progesterone)

Peripheral resistance decreases by 35%

Question 12

what happens to your blood pressure

Answer 12

decrease resistance partly compensated by increase in cardiac output results in a small change in BP

Question 13

what happens to the respiratory system

Answer 13

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

Question 14

what are the effects of cardiovascular and respiratory changes

Answer 14

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)

Question 15

what happens to renal system

Answer 15

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 is common

Question 16

what occurs at the molecular levels in the renal system

Answer 16

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

Question 17

what happens to the GI system

Answer 17

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)

Question 18

what happens to glucose metabolism

Answer 18

First trimester: increased sensitivity to insulin thus mothers increase glycogen synthesis and fat deposition

Second 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)

Question 19

what happens to the folate during pregnancy

Answer 19

DNA synthesis, repair and regulation

• Important in rapid cell division (embryos)
• Deficiency in pregnancy associated with neural tube defects (NTDs)

RBC development
-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

Question 20

what happens to your thyroid function

Answer 20

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

Question 21

what hormones does the placenta produce

Answer 21

Protein hormones:

hCG (human chorionic gonadotrophin)

hPL (human placental lactogen)

hPG (human placental gonadotrophin

CRH (corticotropin releasing hormone)

Steroids:
Progesterone

Oestrogen (oestriol)

Question 22

what happens to the HCG hormone

Answer 22

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
Produced in large quantities by hydatidiform molar pregnancy & choriocarcinoma
Usually significantly lower in ectopic pregnancy & risk of miscarriages

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

Question 23

what happens to the human Placental Lactogen

Answer 23

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

Question 24

what happens to the placental growth hormone

Answer 24

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

Question 25

what happens to the Placental corticotrophin-releasing hormone (CRH)

Answer 25

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

Question 26

what happens to progesterone

Answer 26

Maintains uterine quiescence by decreasing uterine electrical activity

Immune suppressor ( HLA )

Lobulo-alveolar development in breasts

Substrate for fetal adrenal corticoid synthesis eg cortisol

Question 27

what happens to oestrogen

Answer 27

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)