physiology- foetal **INCOMPLETE **

Question 1

through which openings does shunting occur in foetal circulation?

which areas does each shunt connect?

Answer 1

ductus venosus
- directs blood to IVC

foramen ovale
- allows blood to pass from R to L atrium

ductus arteriosis
- connects pulmonary a. to aorta
(carries the output of the R ventricle owing to the higher pressure of the pulmonary vs systemic circulation)

Question 2

in adults:

CO= SV x HR

in foetus how is cardiac output measured?

how does cardiac output compare on 2 sides in foetus?

Answer 2

“combined ventricular output”
i.e. total output of 2 ventricles

2/3 of blood returns to the right ventricle
1/3 to the left ventricle

Question 3

what are the names of the 3 shunts in foetal circulation:

Answer 3

1. ductus venosus - directs blood to IVC
2. ductus arteriosus - connects pulmonary a. to aorta
3. foramen ovale - allows blood to pass from R to L atrium

Question 4

myocardial growth:
i. antenatally
ii. post-natally

Answer 4

i. hyperplasia (^^ no.)
ii. hypertrophy (^^ size)

Question 5

what are the substrates for cardiac metabolism in:

i. adult
ii. foetus

what does the foetus lack which explains for this difference?

Answer 5

i. long chain fatty acids (glc and lactate only in hypoxia)

ii. mainly carbs and lactate

foetus lacks enzyme for transport of fatty acids into micochondria

Question 6

foetal HR
i. what controls it?
ii. stimulated by
iii. inhibitted by

iv. other factors that control foetal HR

Answer 6

i. SA node
ii. sympathetic system
iii. vagal stimulation (parasympathetic)

Question 7

i. what controls BP?

ii. what controls changes in partial oxygen pressure?

Answer 7

i. baroreceptors in the aortic arch

ii. chemoreceptors

Question 8

normal foetal HR at term?

Answer 8

110-150 bpm

Question 9

common causes of foetal tachycardia:
(4)

Answer 9

foetal hypoxia a (where it is accompanied by an evolving picture of loss of beat-to-beat variability and late decelerations)
maternal pyrexia
chorioamnioitis
tocolysis

Question 10

foetal tachycardia:

i. definition

ii. causes (5)

Answer 10

i. HR >110 for 10+ mins

ii.
foetal hypoxia
cord compression
maternal hypotension
uterine hyperstimulation
foetal heart block (v. rarely)

Question 11

beat-to-beat variability
= fluctuation of FHR of at least 2 cycles/ min

increases with gestational age

divided into STV and LTV (short and long-term variability)

Answer 11

short-term variability (STV). In clinical
interpretation these two are usually reported together,
but computerised cardiotocography (CTG) and fetal
electrocardiogram (ECG) can measure LTV and STV
separately. The LTV measures the oscillations or fluctuations of the heart rate within its baseline range (excluding accelerations or decelerations) and it is measured in
cycles/minute. STV is measured in milliseconds and
measures the R–R interval between two consecutive
QRS complexes on the fetal ECG. Although modern
external ultrasound devices use standard CTG to give
a close approximation, STV can only be correctly measured using a scalp electrode. The STV therefore reflects
the change in the FHR from one beat to the next and is
the cause of the rapidly changing display in FHR using foetal scalp electrode monitoring

Question 12

what may cause absent/ reduced variability?

Answer 12

• being pre-term

-foetal sleep cycle
- foetal metabolic acidosis
- drugs (CNS depressants e.g. magnesium sulphate, morphine, alcohol)
- neuro abnormlaity

Question 13

foetal heart accelerations

i. definition

ii. causes

Answer 13

= increase of 15 beats/minute for at least 15 seconds

ii. foetal movement/ stimulation

during contractions - umbillical vein compression

Question 14

foetal heart decelerations

i. definition

ii. subclassifications

Answer 14

i. decrease of 15 beats/minute for at least 15 seconds.

ii.
early - due to uterine contraction
variable - due to cord compression
late - due to hyoxia, bad

Answer 15

pulmonary circuit - high resistance

due to compression of pulmonary capillaries by collapsed lung, the smooth muscle layer of the pulmonary arteries and the vasoconstrictive effects of low fetal partial pressure of oxygen (PO2).

Answer 16

systemic circulation low resistance to blood flow

owing to the large placental bed. The
presence of shunts, high pulmonary resistance and low
systemic resistance allows blood to be diverted from the
lungs to the placenta

Question 17

although oxygenated and deoxygenated blood mix this does not result in homogenous semi-oxygenated blood

Answer 17

preferential streaming of oxygenated blood
occurs from the umbilical vein via the ductus venosus and
foramen ovale into the left ventricle and proximal aorta,
allowing highly oxygenated blood to reach the coronary
and carotid arteries. Deoxygenated blood enters the right
atrium from the inferior and superior vena cava, through
the tricuspid valve into the right ventricle, pulmonary
trunk and ductus arteriosus, entering the descending aorta
and the umbilical arteries. The physiology of the three fetal
shunts allows this preferential streaming of blood

Question 18

ductus venosus

i. what 2 structures does it connect

ii. what is its diameter and what is the benefit of this narrow diamteter

iii. how much of umbilical blood is shunted through ductus venosus at:
A. midgestation
B. 30-40 weeks
^^ why this change?

Answer 18

i. umbillical vein to IVC at the inlet to the heart

ii. 0.5mm (up to 2mm later in gestation). narrow diammeter allows acceleation in blood velocity which allows preferential streaming of ixygenated bloos

iii.
A 30%
B 20%
^^ due to cevelopment of liver which requires larger proportion of imbilical venous blood

Question 19

foramen ovale

i. which 2 structures does it connect

ii. formed by overlap of which 2 structures

iii. which side of foramen ovale has higher pressure? (and in which direction does blood flow in as result?)

Answer 19

i. R and L atrium

ii. overlap of septum secundum over septum primum to produce a flap-valve

iii. R (therefore blood flow is from R–>L

Answer 20

Blood enters the right atrium
from the IVC. Within the IVC, blood flow is not uniform, with the highly oxygenated blood that originated from the umbilical vein flowing anteriorly and to the left
within the IVC. As blood enters the atrium from the IVC, it is divided into two streams by the free edge ofthe atrial septum (the crista dividens). The high-velocity
oxygenated blood is shunted towards the left, through the foramen ovale and into the left atrium. The lower velocity, less oxygenated blood is shunted towards the
right, mixing with blood from the superior vena cava and coronary sinus.
The net result of this is that blood in the left ventricle is more highly oxygenated than in the right ventricle.
The highly oxygenated blood in the left ventricle is pumped into the ascending aorta and 90% of it flows into the coronary arteries, left carotid and subclavian
arteries; the remaining 10% flows via the aortic arch and into the descending aorta, mixing with blood from the ductus arteriosus.

Question 21

ductus arteriosos:

i. which 2 structures does it connect

ii. which structure does the blood therefore bypass

Answer 21

i. pulmonary trunk to descending aorta

ii. lungs

Answer 22

After right ventricular contraction,
blood flows mainly through this vessel and into the
descending aorta, with about 13% of the combined
cardiac output entering the pulmonary circulation, to
support lung development. After 30 weeks, the proportion of blood flow to the lungs increases to about 20% of
the combined cardiac output. The patency of the ductus
arteriosus is maintained by the vasodilator effects of
prostaglandins (PGE1 and PGE2) and prostacyclin
(PGI2) and reduced fetal oxygen tension.

Question 23

via what structure does blood flow from the foetus to the placenta?

what portion of ventricular output does this account for at:
i. 20 weeks
ii. after 32 weeks

Answer 23

umbilical arteries

i. 33%
ii. 20%

NB. resistance to blood flow through the placental vascular beds has no neural regulation and catecholamines have little effect

Question 24

mechanisms which ensure adequate O2 delivery to foetus (3):

Answer 24

1. shunts (ensure preferential delivery of O2 rich blood to myocardium and brain and O2 poor blood to placenta)
2. high HR
3. foetal haemoglobin - results in O2 binding even at low PO2, which results in high saturation even at low O2 tensions

Question 25

transitional events at birth

Question 26

4 key things needed for normal lung development:

Answer 26

1. normal anatomical development
2. foetal breathing movements
3. absorption of lung fluid at birth
4. surfactant production

Question 27

i. 5 stages of foetal lung development
ii. gestation at which this occurs
iii. developmental events

Answer 27

Question 28

foetal breathing movements:

i. may occur from when?

ii. what is their purpose antenatally?

iii. what factors increase foetal breathing movements?

iv. what factors decrease foetal breathing movements?

Answer 28

i. end of 1st trimester

ii. regulation of lung growth by lung fluid regulation and lung cell growth

iii. increase after maternal meal/ glc administration
conditions of acidosis

iv. foetal hypoxia, maternal alcohol and sedative consumption

Question 29

i. from which cells is lung fluid secreted?

ii. at which stage of lung development does this begin?

lung fluid is essential for normal lumg development and reduction in lung fluid or amniotic fluid results in lung hypoplasia

Answer 29

i. alveolar epithelial cella

ii. canalicular

Question 30

i. what type of molecule is surfactant?
what are its components?

ii. which cells produce it?

Answer 30

i. lipoprotein
About 90% is made of lipids, with two-thirds oft his being dipalmitoylphosphatidylcholine (DPPC). The remaining 10% of surfactant is made of proteins, including surfactant proteins A–D.
ii. type II pneumocytes

Question 31

what is the function of surfactant?

Answer 31

reduction of surface tension in elastic recoil

i.e. increasing pulmonary compliance and allowing normal lung inflation

^^ this also prevents lungs from collapsing at the end of expiration

Question 32

i. which component of surfactant is mainly responsible for control of surface tension?

ii. which components of surfactant allow spread of surfactant over alveolar surfaces

iii. which components of surfactant aid innate immunity by their pathogen-recognising functions?

Answer 32

i. DPPC

ii. surfactant proteins B&C

iii. surfactant proteins A&D

Question 33

what substances aid lung maturation?

Answer 33

glucocorticoids mainly

also:
- thyroid hormones
- prolactin
- catecholamines

Question 34

what delays foetal lung maturation?

Answer 34

maternal diabetes (unclear whether this is due to hyperglycaemia or insulin administration)

androgens (this explains why male infants are more likely to experience respiratory distress than females of same gestation)

Question 35

transitional events at birth (RESP)

Answer 35

Even before the onset of labour, lung fluid secretion falls
and reabsorption of fluid from the alveolar spaces
begins. With the first breath of air into the lungs, an
air/liquid interface is created and surfactant facilitates
the formation of the alveolar lining. The pulmonary
fluid continues to be replaced by air and most has been
actively absorbed (across the alveolar wall into capillaries and lymphatics) within 2 hours of breathing. The
transition from fetal breathing movements to normal
ventilation is triggered by a series of tactile and thermal
stimuli. The first breaths are important in inflating the
fluid-filled lungs. These initial inflation breaths generate
pressures that are 10–15 times greater than that needed
for subsequent breathing. Once the alveoli are aerated,
breathing requires minimal negative intrathoracic pressure to maintain a normal tidal volume and alveolar
surface tension is stabilised by the surfactant released by
distension and ventilation of the lungs.

Question 36

3 periods of foetal haematopoeisis and periods they occur in:

Answer 36

1. mesoplastic
   - in yolk sac from 14 days to 12 weeks
2. hepatic
   - 6 to 18 weeks (peaks 10 to 18 weeks)
   - at this point liver = main source for foetal haematopoeisis
3. myeloid
   - from 8 weeks to adulthood
   - blood bells developing from stem cells which 1st appear in yolk sac but migrate to foetal tissues where they give rise to primitive cells then definitive ones

Question 37

foetal RBC proudction occurs independently of mother and is controlled endogenously

difference between primitive & definitive RBCS

Answer 37

embryonic haemoglobin is not controlled by erythropoietin (EPO)

definitive red blood cells containing mainly fetal haemoglobin (HbF)
are regulated by EPO

Question 38

where is foetal EPO produced?

Answer 38

initially liver then kidneys

Question 39

what causes increased foetal EPO production?

Answer 39

hypoxic conditions

e.g. placenta insufficiency, severe maternal anaemia

Question 40

at what gestation does foetal WBC production begin?

where does it occur?

Answer 40

6 weeks

initially in liver, also spleen, thymus, lymphatic system

Question 41

granulocyte concentration in neonate vs adult?

Answer 41

equal or greater than in adult

Question 42

platelet production

i. at which gestation does it start?

ii. where does it occur?

Answer 42

from 6 weeks in yolk sac
from 8 weeks in liver

Question 43

Hb structure
i. in adult
ii. in foetus - embryonic haemoglobins

Answer 43

i. 2 alpha and beta chains

ii. HbGower 1, HbGower 2, HbPortland
^^ are replaced at 10 weeks by HbF which consists of 2 alpha and 2 gamma chains

Question 44

HbF

i. is the dominant Hb from which gestation?

ii. peaks to which % at which week?

iii. % present at birth

iv. until how long post-natally is it present?

Answer 44

i. 10 weeks

ii. >90% tat 32 weeks

iii. 60-80%

iv. 3-6 months

Question 45

HbA (adult haemoglobin)

i. which gestation is it present from?

Answer 45

10 weeks, becomes predominant Hb from 12 weeks post-natal

Question 46

which of HbF/ HbA has better O2 binding affinity?

why?

Answer 46

HBF

HBA binds with 2,3-diphosphoglycerate (2,3-DPG) which reduces its O2 binding affinity

Question 47

which of HbF/ HBA is more resistant to alkali denaturation/ acid elution?

Answer 47

HbF is more resistant

This forms the basis of the Kleihauer test

Question 48

how does Kleihauer test work?

Answer 48

1. maternal blood smear is taken and acid bath removes HbA
2. HbF is stained to allow:
   - pink foetal-stained cells to be viewed under microscope
   - HbA-containing maternal cells appear as ‘ghost cells’
3. counting above allows estimation of the amount of foetal blood in the maternal circulation as may occur following maternal-foetal haemorrhage

must consider persistence of maternally derived HbF - this can occur in haemoglobinopathies and may affect results/ interpretation

Postnatally the ability of the Kleihauer test to assess fetal
red cells in the maternal circulation will depend on thepersistence of the cells. If the mother and fetus are ABO,incompatible fetal red blood cells may be eliminated from the maternal bloodstream very quickly and a Kleihauer test should be performed as soon as possible in
these circumstances

Question 49

where do precursors of foetal immune system develop and migrate to?

what do lymphoid stem cells giev rise to?

Answer 49

yolk sac, liver, spleen, bone marrow, thymus

B lymphocytes (from liver)
T lymphocytes (from thymus)

Question 50

from which gestation do the following appear in the blood?

i. B cells
ii. mature T cells

Answer 50

i. 12 weeks
ii. 14 weeks

Question 51

at which gestation does immunoglobulin synthesis start?

which Ig increases at 12 weeks as it crosses placental barrier?

rise of which Ig is suggestive of intra-uterine infection as it does not cross placental barrier?

at which gestation is immune system same as for term infant?

Answer 51

12 weeks

IgG

IgM

32 weeks

Question 52

foetal immune development - changes at birth

Answer 52

The neonatal blood parameters change depending on
the degree of placental transfusion. Late clamping of the
cord and holding the newborn below the level of the placenta results in a significant increase in blood volume
and red blood cell mass. Whether this is of benefit is
controversial. In preterm infants it has been suggested
that hyperbilirubinaemia may result from excessive placental transfusion; however, hypovolaemia may result if
immediate clamping occurs. Haemoglobin levels in
newborns are usually around 16.5–17.5g/dl with a
haematocrit of around 53% and mean white blood cell
counts are 15000/mm3
. Red blood cell and white blood
cell counts increase in the initial hours after birth before
decreasing by day 4–7. Platelet counts are similar to
adult values but increase throughout the first month of
postnatal life. Platelet activity is reduced in the neonate
and the risk of bleeding and coagulopathy is increased,
particularly in preterm infants. This is compounded by
the low levels of vitamin K-dependent clotting factors

Question 53

foetal renal physiology

i. gestation at which urine production starts

ii. gestation at which reabsorption by loop of Henle starts?

iii. how much of CO goes to kidneys in foetus vs adult?

Answer 53

i. 9-10 weeks

ii. 12 weeks

iii. 2-3% (vs 20% in adult)

Question 54

which structure controls foetal fluid and electrolyte
balance?

Answer 54

placenta

Question 55

what is main constituent of amniotic fluid

i. before 16 weeks
ii. after 18 weeks

Answer 55

i. fluid produced by skin & placenta
ii. foetal urine

reduced urine production from midgestation is an
important cause of reduced amniotic fluid volume and
can be seen in fetal growth restriction

Question 56

tonicity of foetal urine?

why?

from which gestation is no. of nephrons = to adult?

Answer 56

hypotonic

foetal kidney has limited ability in concentrating urine

[ability to concentrate urine increases with gestation]

34 weeks
- functional maturity is not established until post-natally
–> therefore infants are less able to maintain fluid and electrolyte balance

Question 57

RENAL
transitional events at birth

Answer 57

After birth, there is a dramatic increase in renal blood
flow to the kidney, increasing from 2–3% of combined ventricular output in the fetus to about 10% of cardiac
output at age 4 days. With renal blood flow, glomerular
filtration rate also increases at birth and this continues
with a doubling by 2 weeks of neonatal life.