L18 Physiology of Pregnancy

Question 1

Volume homeostasis

Answer 1

Rapid increase in plasma volume by 40%

• 2.5L to 3.7L by end of pregnancy
• 11-13kg weight gain (8-10kg fluid)

Plasma colloid osmotic pressure

• causes a shift of fluid into extra cellular space
• increased hydration of connective tissue
• oedema (lower limbs, hands and face)

Question 2

Mechanism of increased plasma volume

Answer 2

Slight decrease in atrial natriuretic peptide ANP

Decreased thirst threshold (increased fluid intake)

Re-setting osmostat

INCREASED PLASMA VOLUME

Question 3

What happens to red blood cells during pregnancy?

Answer 3

Haemoglobin

• red cell mass increases by 25% (1.3L to 1.7L)
• plasma volume increases by 40%
• 13.3 to 10.9 g/dL at 36 weeks
• dilutional anaemia

Question 4

Iron in pregnancy

Answer 4

Iron is required for the increased red cell mass

• fall in ferritin levels
• increased iron absorption from gut

Question 5

When do you need to give Fe supplementation?

Answer 5

twin pregnancy

Question 6

What happens to the delivery of blood to the uterus?

Answer 6

Uterine artery blood flow increases 3.5 fold from 95 to 342 ml/min

Question 7

Haemostats in pregnancy

Answer 7

Hypercoagulable state
-increase plasma fibrinogen (increased ESR), platelets, factor VIII & von willebrand factor

Marked effect at delivery

• 500ml/min blood loss at placental separation
• myometrial contraction - 10% of all fibrinogen used up

Evolutionary balance between thrombosis and haemorrhage

Question 8

White blood cells during pregnancy

Answer 8

Concentration does not fall during pregnancy

Total WBC increases in pregnancy

Increase in neutrophils (reduced apoptosis)

Marked increased around delivery

Question 9

Increased blood volume during pregnancy has implications on

Answer 9

Cardiac output

Peripheral resistance

Blood pressure

Question 10

Cardiac output =

Answer 10

SV x HR

Increased SV required increased heart volume

Question 11

Heart changes during pregnancy

Answer 11

Heart enlarges by 12% (increased venous return)

Innocent systolic murmurs are common (approx 90%)

Diastolic murmurs (approx 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 x-ray

Question 12

What happens to peripheral resistance during pregnancy?

Answer 12

Peripheral vasodilation (effect of progesterone)

Peripheral resistance decreases by 35%

Question 13

Effect of pregnancy on BP

Answer 13

Decreased peripheral resistance compensated by the increase in cardiac output

results in small change in BP

Question 14

Effect on respiratory system

Answer 14

increased pulmonary blood flow matched by

increase tidal flow

decrease maternal pCO2 and increase maternal pO2

increased availability of O2 to tissues and aids passive diffusion at the placenta i.e. higher concentration gradient

Question 15

Effects of cardiovascular & respiratory changes

Answer 15

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 16

Effect of pregnancy on renal system 1

Answer 16

Kidney increases 1cm size during normal pregnancy

GFR and effective renal plasma flow increase 50+%

BUT tubular reabsorption capacity is unchanged
- leads to decrease in glucose reabsorption thus glycosuria is common

Question 17

Effect of pregnancy on renal system 2

Answer 17

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 18

Effects on GI

Answer 18

Gastro-oesophageal reflux up to 70 %
- due to increase abdominal pressure, reduced pyloric sphincter with back wash of bile secondary to hormonal changes

Slowing of gut motility and constipation (progesterone effect)

Question 19

simple measures to reduce reflux

Answer 19

avoidance of fat and alcohol

upright posture and antacids

Question 20

effect on glucose metabolism: 1st trimester

Answer 20

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

Question 21

effect on glucose metabolism: 2nd trimester

Answer 21

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 22

Effects on folate: DNA synthesis, repair and regulation

Answer 22

Important in rapid cell division (embryos)

deficiency in pregnancy associated with neural tube defects

Question 23

Effects on folate: RBC development

Answer 23

macrocytic anaemia

Question 24

daily folate requirement increases from what to what

Answer 24

50mg to 400mg

Question 25

plasma folate represents

Answer 25

current nutritional status but significant tissue stores e.g. liver - RBS folate is a good biomarker (no change in pregnancy)

Question 26

no need for folate supplementation BUT

Answer 26

prevents neural tube defects this routinely given preconception to 3 months

Question 27

effect on thyroid function

Answer 27

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 28

placenta as what kind of organ

Answer 28

endocrine

Question 29

placenta: protein hormones

Answer 29

hCG (human chorionic gonadotrophin) hPL (human placental lactogen) hPG (human placental gonadotrophin CRH (corticotropin releasing hormone)

Question 30

placenta: steroid hormones

Answer 30

progesterone oestrogen

Question 31

Human chorionic gonadotrophin (hCG; 1 of 2)

Answer 31

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

Question 32

Human chorionic gonadotrophin (hCG; 2 of 2)

Answer 32

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 33

Human placental lactogen (hPL)

Answer 33

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 34

Placental growth hormone (hPG)

Answer 34

Placental Growth Hormone secreted by the placenta responsible for regulating fatal growth Induces maternal insulin resistance No evidence of that maternal GH or fetal GH required for fetal growth

Question 35

Placental corticotrophin-releasing hormone (CRH)

Answer 35

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 postpartum Increased cortisol can result in increased maternal glucose

Question 36

Progesterone

Answer 36

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 37

Oestrogen

Answer 37

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)