S4: Adaptation II Flashcards

1
Q

Describe exchange between foetal and maternal circulation at the placenta

A
  • During intrauterine life, the foetus is totally dependent on the mother to maintain life, this is in terms of provision of nutrients and in the removal of waste products.
  • The starting point of the foetal circulation could be said to be at the placenta which is embedded in the uterine wall and is partly maternal and partly foetal.
    At the placenta there is exchange of oxygen and nutrients from maternal to the foetal circulation and waste products move out from the foetal circulation to the maternal circulation.
    Note however that the two circulations do NOT mix.
  • The finger like projection capillaries of the foetal circulation push inwards into the pool of maternal blood separated by thin membranes. These are the placental villi. It is here that there is transfer of substances between the foetal capillaries and maternal blood pool. Deoxygenated blood containing waste products enters in the umbilical artery and is high CO2 and waste, this diffuses into the maternal circulation. Blood from the mother is high in O2 and nutrients and these diffuse into foetal capillaries, the oxygenated and nutrient rich blood returns back through the umbilical cord being carried in the umbilical vein.
  • This is how the foetus exchanges and therefore is not reliant on its lungs until after birth.
  • Note of the oxygenated and nutrient rich blood in the umbilical vein, some will enter into the foetal liver and some shunted into the IVC mixing with deoxygenated blood. This mixed blood will enter into the right atrium
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2
Q

Describe structure of haemoglobin (adult and foetal)

A
  • Oxygen is carried in the blood in two forms, dissolved in plasma and the erythryocyte water (2%) and reversibly bound to Hb the oxygen carrying pigment (98%).
  • Adult Hb is composed of four polypeptide chains, 2 alpha and 2 beta. Each is associated with a haem group containing porphyrin ring and ferrous Fe2+. Oxygen binds to the iron reversibly and thus four molecules of O2 can bind to a single Hb. When PO2 is high it will bind, when PO2 the oxygen will dissociate.
  • Foetal Hb on the other hand consists of two alpha chains and two gamma chains and has different properties to adult Hb.
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3
Q

Describe how different globin chains are synthesised at different types through development and by different organs at different times

A
  • It can be seen that very early on in gestation it is the yolk sac that synthesises Hb, but then by about 6wks the liver takes over.
  • The alpha Hb chain and gamma Hb chain are synthesised the most. While epsilon and chi fall quite rapidly in early gestation.
  • Nearing birth the spleen starts to take over more and more and there starts to be a fall in gamma Hb. Beta Hb starts to increase and then at birth, beta shoots up and gamma nosedives down.
  • Now bone marrow takes over as the synthesiser of Hb and erythrocytes.
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4
Q

Difference adult and foetal Hb

A
  • Foetal Hb is different to adult Hb and this is necessary in order to perform its function and keep the foetus alive.
  • Foetal Hb has a much higher affinity for O2 than adult Hb, this means that it continues to bind O2 at lower partial pressures and therefore is more saturated at lower partial pressures than adult Hb.
  • This can be seen by the oxygen dissociation curve being shifted to the left for foetal Hb, meaning it is more “sticker” with O2 and holds it tighter.
  • For the same amount of oxygen fetal Hb is more saturated.
  • For example at 5 kPa, adult Hb is only about 50% saturated whereas foetal is around 80% saturated. This stronger affinity for O2 allows oxygen to be transferred from mother to baby across the placenta. As the mothers venous blood at 5kPa will let go of O2 and it will be sucked up by the foetal Hb at the same partial pressure.
  • Interestingly this difference in affinity is caused by only a single AA change!
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5
Q

Describe role of2.3 diphosphoglycerate

A
  • 2.3 diphosphoglycerate promotes release of oxygen.
  • In adults and older children 2,3 DPG binds to deoxygenated Hb and promotes further release of the remaining O2 and it also makes it harder for O2 to bind. Thus it shifts the oxygen dissociation curve to the right, so Hb will release O2 at higher partial pressures of O2.
  • In pregnant women there is a 30% increase in 2,3-DPG so their Hb has LESS affinity for oxygen and allows more O2 to be offloaded at the placenta and given to the foetus.
  • Foetal Hb doesn’t bind 2,3-DPG as well as adult Hb does, therefore this further enhances HbF affinity to oxygen as the curve is shifted to the left.
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6
Q

Describe the foetus circulation to and from the heart

A
  • Going back to the circulation from the placenta it was discussed how oxygenated, nutrient rich blood leaves the placenta returning to the foetus in the umbilical vein. This has a Hb saturation of 80-90% and oxygen partial pressure of about 4.7kPa (high saturation due to HbF affinity!).
  • The umbilical vein travels up towards the liver, however around 50-60% of the blood in it will bypass the hepatic circulation and be shunted into the IVC via the ductus venosus. The rest will enter into the portal vein.
  • The oxygenated blood from the umbilical vein combines with the deoxygenated blood (25-40% saturation) coming up in the IVC from the legs. Thus the blood in the IVC is now mixed blood and it enters into the right atrium where blood from the SVC also flows in.
  • Once in the RA the mixed blood has two options, it can either be pumped down into the right ventricle or get shunted through the foramen ovale in the interatrial septum into the left atrium. The majority of blood will take the latter route.
  • The lungs are still developing and are filled with fluid, and not ready for gas exchange so the lung capillaries are vasoconstricted meaning there is high pressure and high resistance in the pulmonary artery/circulation. This leads back to high pressure in the right ventricle and hence right atria. This pushes blood through the foramen ovale and into the left atrium. It then enters into the left ventricle and is pumped out into the aorta.
    In this way the foetal circulation has bypassed the lungs.
  • For any blood that happens to enter into the RV, it will be pumped into the pulmonary artery. In order to reduce the amount going to the lungs, there is a vessel connection the ductus arteriosus that connects the pulmonary artery to the aorta. Any blood that enters into the pulmonary artery gets shunted into the aorta, again preventing blood going to the lungs. Thus very little blood returns to the LA via the pulmonary veins.
  • % Saturation in the LA is about 65%, this is high enough for the myocardium and brain to get blood with high oxygen.
  • We can see it is mixed blood that passes around the body. One branch of the internal iliac arteries is the umbilical artery, a proportion of blood will enter into this and travel to the placenta where it will have CO2 and waste removed and become oxygenated and get nutrients.
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7
Q

Summary of foetal circulation

A

Oxygenated blood through umbilical vein –> IVC –> Right atrium –> Left atrium –> Left ventricle –> Aorta –> Preferentially streamed to brain and myocardium so most oxygenated blood goes to heart and brain.

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8
Q

Difference foetus and adult circulation

A
  • Ductus venosus; Connects placenta and IVC via L umbilical vein.
  • Ductus arteriosus: Connects pulmonary artery and aorta.
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9
Q

Describe changes to baby circulation system at birth

A
  • Once the baby is delivered, the circulatory system that was present during intrauterine life needs to rapidly adapt to extrauterine life.
  • The two big events that occur at birth are the placenta gets removed from its connection with the baby and the lungs start to take in air.
  • When the umbilical cord is clamped exposure to the cooler temperatures cause the umbilical vessels to get constricted. Therefore blood is no longer flowing into the umbilical vein or ductus venosus so it closes over 3-10 days. Thus the placental circulation ceases. This means there is no more mixed blood in the IVC, it is all deoxygenated.
  • At birth the baby starts to breathe after birth, remaining fluid in the lung gets pushed out and is now filled with air. The oxygen causes the pulmonary arterioles to dilate and resistance in the pulmonary circulation falls massively leading to an 8-10x increase in blood flow in the pulmonary circulation. With the lower resistance and pressure in the pulmonary circulation it means that pressure in the RV and RA are now lower. Due to the decrease in pulmonary circulation resistance, more blood is flowing through and this means more blood is returning to the LA via the pulmonary veins. As a result the pressure in the LA increases massively. As a result the RA and LA pressures equalise and the flap of the foramen ovale gets pushed against the interatrial septum and this closes of the shunt. The foramen ovale closes off within minutes to hours of birth.
  • The fall in pulmonary artery resistance and thus pressure leads to blood now flowing both ways (bidirectional) in the ductus arteriosus. Ultimately the rise in oxygen tensions and a fall in prostaglandins (produced by placenta, as placenta now removed from circulation) cause the ductus arteriosus to close. Thus this shunt is also closed off. This is closed in 96 hours.
    Once closed off it is called the ligamentum arteriosum.
  • Closure of the foramen ovale and ductus arteriosus means that all deoxygenated blood entering the right atrium enters into the right ventricle and all enters the pulmonary arteries and goes to the lungs. Blood now returns oxygenated to the left atrium is pumped into the left ventricle and enters into the aorta. Now fully oxygenated blood is travelling in the aorta and the saturation and partial pressure of oxygen is much higher (13kPa O2).
  • The umbilical artery that comes off the internal iliac will have very little blood flowing into it as it constricts due to low prostaglandins and higher oxygen tensions.
    Eventually it will close off.
  • Note that these changes start very soon after birth and are initiated in essence by the breathing in of air into the lungs that increases oxygen pressures in the blood and dilates the pulmonary circulation.
    As well as the placenta being removed from the circulation and the umbilical vessels closing off.
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10
Q

Summary baby circulation system at birth

A

Disconnects baby from placenta –> no blood through ductus venosus –> Baby takes a breath –> Pulmonary vessels open up –> Increased oxygen levels also opens blood vessel –> More blood flow to lungs –> More to left atrium –> Causes connection between right and left to close

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11
Q

List abnormal circulation when born

A

Pulmonary vessels stay narrow. Patent Ductus Arteriosus. Atrial septal defect.

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12
Q

Describe pulmonary vessels staying narrow in abnormal circulation

A

Sometimes the transition to extrauterine life may not be permanent as the pulmonary arterioles are very reactive and may end up constricting again due to exposure to certain stimuli like: Hypoxia, Hypercarbia, Acidosis and Cold. This can result in a rise in pulmonary venous pressure, causing right to left shunting.
- Pulmonary vessels stay narrow.

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13
Q

Describe patent ductus arteriosus in abnormal circulation

A
  • Patent ductus arteriosus is where the ductus arteriosus fails to close after birth. This leads to oxygenated blood that has just entered into the aorta (where pressure is higher) from the LV flowing back into the pulmonary artery and going to the lungs.
  • Early symptoms are uncommon (asymptomatic) but a continuous machinery murmur can be heard. In the first year of life it can lead to more work of breathing and if uncorrected can lead to congestive heart failure. Symptoms of heart failure include: Fast breathing, Increased work of breathing, Sweating during feeding, Poor feeding, Poor growth, Rapid pulse, Bounding pulse. This is because the moving of blood into the pulmonary arteries increases blood to the lungs to too much, this increases the pressure in the lungs making them harder to inflate.
  • PDA is common in: Premature babies, Babies with respiratory distress (due to being hypoxic), Downs syndrome babies, Rubella infection and Congenital heart disease.
  • Treatment of PDA include indomethacin, an NSAID that inhibits production of prostaglandins and therefore encourages the duct to close. Ibuprofen is another option. Sometimes surgery may be used to ligate the vessel.
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14
Q

Describe atrial septal defect in abnormal circulation

A
Potential ASD include:
- Ostium primum defect.
- Ostium secundum defect.
- Sinus venosus defect.
- Common atrium.
- Patent foramen ovale.
Result in acyanotic shunting. If small may be asymptomatic. However more complex ones can lead to heart failure, stroke etc. Shunting will be audible with auscultation. Can treat with ibuprofen but only works around 2/3rds of the time. If hole is much bigger and wont close may need to close operatively.
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15
Q

Describe thermaregulation in newborns

A
  • Neonates are at increased risk of heat loss because they have a high surface area to body mass ratio compared to adult so more likely to get cold. They also lack thermal insulation such as having lower % body fat and less subcutaneous fat. They are also unable to utilise additional methods of remaining warm e.g. clothing or moving to a warmer area. Thus neonates must have mechanisms in place to protect them from falling into hypothermia which is very deadly!!
  • In order to maintain body temperature thermogenesis is required. Thermogenesis is the production of heat within the body. Neonates cannot shiver, therefore they rely on non-shivering thermogenesis and this is through the use of brown fat. So neonates produce extra brown fat and use a lot of energy to porduce heat.
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16
Q

Describe brown fat in neonates

A

Brown fat contains very high numbers of mitochondria that are unique to other tissues. The mitochondria in brown fat have uncoupled the movement of protons down their gradient (from intermitochondrial space to matrix) to the production of ATP (uncoupling of oxidative phosphorylation). Instead the movement of protons down their gradient results in production of heat. This is done by uncoupling protein.

  • This process is controlled by the sympathetic innervation of brown fat, it is also highly vascularised in order to warm the blood.
  • This is important as hypothermia makes a baby much more likely to die. Indeed it is one of the main causes of neonatal death.
17
Q

Describe mechanism of heat loss

A
Evaporation = Heat loss through wet skin.
Convection = Heat loss caused by cooler air circulating around/over warm skin, esp. when exposed.
Conduction = Heat loss through direct contact with a cold surface.
Radiation = Heat loss caused by heat radiating towards a cooler surface e.g. towards a window.
18
Q

Ways to keep neonates warm

A

As heat can be lost through wet skin by evaporation drying of the baby is vital after delivery! Other methods to keep baby warm include skin-skin contact, giving a hat, wrap/cover in a plastic bag to warm by humidity. This is very important in neonates who are especially at risk of hypothermia. Also keep room temperature warm.
- A thermoneutral environment is the optimum environmental temperature to ensure the lowest oxygen and energy expenditure.
The thermoneutral range varies with age and also whether the baby is naked or dressed.
If naked range is 32-35 degrees, if dressed 24-27 degrees.

19
Q

What is thermal stress?

A

Thermal stress is the energy needed to maintain a normal body temp, the colder the temperature the greater the thermal stress as body metabolism needs to increase in order to warm the body.

20
Q

Describe fluid balance in neonates

A

Neonates have a very high total body water, this volume decreases with age as muscle and fat increases. Also before birth most of the volume of water is extracellular with less intracellular. However ECFV decreases and ICFV increases as the foetus nears birth, by around 6 months ICFV is higher than ECFV.

  • Epidermis is thinner in preterm baby, stop us losing excess water.
  • In terms of the kidneys, there is full completion of the 1 million nephrons in each kidney by 34 weeks. However they are functionally immature at birth meaning there is a reduced GFR.
  • The renal tubule in neonates also has a limited concentrating ability as the transporters have not reached optimum function in order to move Na+ and glucose out of the tubule (e.g. in LoH) and into the blood and therefore create a gradient for water to diffuse across and be reabsorbed into the interstitial space. Thus it has a limited concentrating ability.
21
Q

Ways fluid is lost

A
  • Fluid can be lost from the respiratory tract. This depends on the temperature and also the humidity of inspired gas. Also the respiratory rate, tidal volume and amount of dead space will influence fluid loss.
    Fluid is also lost via the kidneys and stool.
  • Fluid can also be lost from the skin, in preterm babies the skin isn’t fully developed and therefore fluid loss from the skin can be extremely high. Therefore the more premature a baby the greater the fluid loss! This transepidermal water loss,
22
Q

What is gestational age and post natal age?

A

Gestational age gives the week of delivery. Post-natal age is the days after delivery, we can see slowly as the baby ages the skin does mature and fluid loss is less.

23
Q

3 things adaptation to extrauterine life involves

A
  1. Modifying the foetal circulation
  2. Correct temperature control
  3. Fluid balance