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Medsci 312 > Lecture 12; Fetal Growth Part One > Flashcards

Lecture 12; Fetal Growth Part One Flashcards

1
Q

Do the essential reading

A

Now

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2
Q

Describe the size of babies

A

Babies come in a range of sizes.

  • Small for Gestational Age (SGA) <10% percentile
  • Appropriate for gestational age 10< X < 90 percentile
  • Large for gestational age (LGA) 90+ %

All at time of delivery

Undergrowth vs overgrowth (birthweight)

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3
Q

What does growing a baby in 40 weeks take?

A

Lots of feeding

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4
Q

Describe the rates of growth over time in gestation

A

12-14 weeks of rapid accelerating growth rate then decline (12-24 week is rapid acceleration in growth velocity)

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5
Q

Broadly describe the nutritional needs of the feotus;

A

Large energy requirement for intrauterine growth, vs.

Little facultative (optional or discretionary) energy needed vs adults (e.g., movement, digestion, or temperature regulation)

Faculative = Mum regulates the body temperature of the baby so they do not need to expend energy on this

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6
Q

What does the foetus need? (broad)

A
  • Carbohydrates, fats, proteins, others

macros and micros

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7
Q

What is the two major purposes of the fetus acquiring nutrients?

A
  1. Accretion of substrates for storage and to build new tissue
  2. To fuel oxidative metabolism
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8
Q

Where does the primary source of nutrients for the feotus come from?

A

Primary source of nutrients is in the maternal circulation

but also

  • Nutrients can be synthesised by the fetus
  • Can be swallowed from amniotic fluid
  • From the placenta
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9
Q

Describe the feotal supply line and variables;

A 
Maternal diet (enters maternal circulation)
- Maternal metabolic and endocrine status influence circulating levels of nutrients

Uterine blood flow
-Placental transport and metabolism (placenta needs nutrients too)

Umbilical blood flow
- Feotal metabolic and endocrine status

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10
Q

Do small changes in maternal circulating nutrients particularly affect the foetus?

A
  • Fetal supply line mediates differences btwn maternal and fetal nutrition.
  • Fetal supply line has enormous reserve capacity
  • Thus, relatively small changes in maternal nutrition do not appreciably alter fetal supply
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11
Q

What are the three routes of foetal nutrient supply?

A
  1. Transported across the placenta from the mother
  2. Synthesised in the placenta and released into the fetal circulation
  3. Produced endogenously by fetal tissues
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12
Q

Describe the placentas role;

A
  • A temporary organ
    • Formed by apposition and fusion of tissues derived from the mother and the conceptus
    • The placenta is the site for nutrient and waste exchange

The placenta also requires nutrients to remain alive

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13
Q

How can nutrients be transported across the placenta?

A
  1. Simple diffusion across cell membranes (egO2, CO2, urea)
  2. Paracellular diffusion between cell membranes
  3. Active and facilitated (eg glucose and lactate) transporter-mediated transfer
  4. Endocytosis-exocytosis across the cell layers
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14
Q

What does paracellular mean in terms of the placenta?

A

Paracellular: transfer of substances across an epithelium by passing through the intercellular space between the cells

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15
Q

What determines how the nutrient is transported across the placenta?

A

The mechanism of transport depends on the substrate’s physiochemical properties

Small molecules such as respiratory gases generally cross the placenta by simple diffusion

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16
Q

What is placental transfer limited by?

A

transfer is limited by placental and uterine blood flow

Also by the consumption of nutrients by the placenta

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17
Q

What is the main substrate transported across the placenta?

A

Glucose

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18
Q

What drives the tranposrt of glucose across the placenta?

A

• The maternal-fetal glucose gradient drives maternal glucose into the fetus

The gradient between the placenta and the fetus also determines if the glucose goes to the fetus or the placenta

Therefore prolonged malnutrition = placental underdevelopment

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19
Q

What controls foetal glucose metabolism?

A

Placenta controls fetal glucose metabolism

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20
Q

What can glucose be converted to in the placenta, that is then transported to the fetus?

A

Glucose can be converted into fructose and pyruvate -> lactate

Intentional aerobic lactate production

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21
Q

What else is importantly transported across the placenta?

A

Amino Acids

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22
Q

Describe placental glucose metabolism

A
  • A large portion of glucose taken up by the placenta is consumed by placental tissues
  • Fetal glucose concentrations can regulate placental glucose consumption independent of maternal concentrations
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23
Q

Describe the relationship between fetal glucose concentration and placental glucose consumption;

A

Glucose is transported to the fetus down a concentration gradient.

Fetal glucose concentration determines placental glucose transfer and consumption.

o High fetal glucose concentrations,net diffusion from placenta to fetus decreases and placental glucose consumption increases

o A reciprocal effect occurs at low concentration.

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24
Q

How does the placental contribute to the control of fetus blood glucose?

A

• The placenta contributes to the control of fetal metabolism by converting glucose and fructose into lactate

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25
Q

What can the fetus use lactate for?

A

– lactate can be used directly by many fetal organs
• Lactate is produced in large amounts
– normal process even during aerobic metabolism

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26
Q

In what situation does placental lactate production increase?

A
  • Lactate production rises with increases in umbilical glucose uptake
  • It is possible under certain conditions that amino acids may be converted to lactate in the placenta
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27
Q

What happens to lactate produced by the placenta?

A

• Lactate produced by the placenta is released into the uterine as well as the umbilical circulation

28
Q

What does fructose do for the fetus?

A

• Fructose is found in the fetus in several species
– produced from glucose in the placenta

• Fructose makes very little contribution to fetal metabolism overall, either as a source of energy or of carbon for accretion of new tissue

29
Q

How does the fetus acquire AA?

A

• The majority of amino acids (a.a.) required by the fetus are derived from mother.
• Amino acid transport occurs by energy-dependent processes via specific transporter proteins
– unique cycling of particular a.a.’s

30
Q

Describe the correlation of serine;

A
  • Placenta takes up a lot of serine (maternal serum serine correlates with neonatal birthweight)

Important nucleotide precursor

31
Q

Describe serine transport across the placenta;

A
  • Placenta takes up a lot of serine
  • Very little maternal serine is transported directly to the fetus
  • Serine is converted to glycine in the placenta
  • Glycine is transported to the fetus, the feotal liver converts it to serine

Serine/glycine cycling

32
Q

Why is serine not directly transported?

A

likely to be an important part of fetal-placental interactions necessary for fetal growth

33
Q

What amino acids are used in late gestation abundantly?

A

Glutamate plus glutamine are among the most abundant and the most utilised amino acids in fetus during late gestation.

34
Q

Describe the importance of serine in the palcenta;

A

One-carbon metabolism, or methyl transfer (via hydroxymethyltransferases), is critical for metabolism in all cells. Serine is the primary endogenous methyl donor to the one carbon pool.

35
Q

What other AA are cycled?

A

Ser/Gly
Glutamine/Glutamate
Leucine

36
Q

Are FAA transported across the placenta?

A
  • Most placental lipid transport is dependent on the maternal-to-fetalplasma lipid concentration gradient
  • The placenta can synthesise FFA and cholesterol in a number of species
37
Q

What is a major hormone present in pregnancy?

A

Placental Lactogen, produced by the placenta

38
Q

How may the placenta influence pregnancy?

A
  • The placenta produces hormones that can influence fetal nutrition by influencing fetal and maternal nutrient supplies
  • i.e placental lactogen which promotes fetal growth
39
Q

What sort of action does placental lactogen have?

A

Has anti-insulin action ;contributes to maternal insulin resistance

i.e increases maternal blood glucose to generate the maternal fetal gradient and drive the transport

40
Q

What does placental lactogen do and what is another important hormone?

A

•
Increases the availability of glucose and other nutrients in the the maternal circulation for transfer to the fetus ,where as FFAs are utlilised as metabolic fuel for the mother
•
GH-variant (or GH-2) produced by placenta is also associated with fetal growth

41
Q

How can where and how much nutrients being produced be determind?

A

Fick principle

The essence of the principle is that blood flow to an organ can be calculated using a marker substance

42
Q

Describe how the fick principle can be used?

A

Using a marker substance and monitoring the arteriole and venous blood, blood supply to an organ can be calculated and/or the nutrient uptake of the organ

43
Q

Describe how the fick principle can be applied to determine fetal nutrient uptake;

A

Blood glucose to fetus = Blood glucose leaving fetus + glucose consumed

Glucose entering
= umbilical blood flow (F, ml/min) x umbilical venous glucose levels [V], umol/ml

Glucose leaving
= umbilical blood flow (F , ml/min) x umbilical arterial glucose levels [A], umol/ml

Thus: F[V] = F[A] + fetal glucose uptake

Thus: fetal glucose uptake (ie umbilical uptake) = F([V] –[A])
i.e.Concentration in umbilical vein –umbilical artery, multiplied by umbilical blood flow

44
Q

How can we determine the placental uptake using fick?

A

Placental uptake =
uterine uptake –umbilical uptake

Uterine uptake = uterine blood flow ([MA] –[UV])

[MA, maternal arterial] –[UV, uterine venous]
= arterial-venous difference

45
Q

What nutrient cant the fick method be applied to?

A

The method is not applicable for measuring fetal urea production because of the small AV differences across the umbilical circulation; instead infuse radiolabelled urea

46
Q

Described urea clearance calculation;

A

-Urea clearance = umbilical blood flow x (A–V) / A-MA

Where A-V –arteriovenous difference of [14C] urea (ie disintegrations per minute of 14C urea) across the umbilical circulation

And A-MA is the umbilical-maternal arterial concentration difference of [14C] urea

47
Q

What are the advantages and disadvantages of the fick method?

A

Advantages of using the Fick principle:

  • Simple
  • Can do repeated measurements

There are also disadvantages of using the Fick principle: not suitable for small A-V differences

48
Q

Describe the partial pressure of fetal oxygen;

A

Fetal arterial PO2(amount of O2 dissolved in the blood ) values are lower than those in the mother

Fetal human PO2is ~ 35 mmHg

Maternal human ~ 95 mmHg

49
Q

How exactly does the fetus obtain oxygen

A

•

Adequate O2supply to the fetus is achieved by relatively high tissue perfusion + fetal O2affinity > mother

50
Q

How can oxygen consumption be determined?

A

Fick principle

Oxygen uptake by the uterus is usually > fetus
– NB Uterine blood blood flow is an important determinant of placental oxygen transfer.

• Placental O2 consumption > fetus

51
Q

Describe foetal glucose requirements

A

Glucose is the major oxidative substrate consumed by the fetus(requires 4-8 mg/kg/min).

52
Q

How does the fetus obtain glucose?

A

(1) Mother (i.e. placenta)
– Greater maternal levels greater feta luptake!
– Fetus is constrained…

(2) Endogenous production

53
Q

Why is the fetus constrained in its glucose uptake?

A

Constrained by the concentration of glucose in the maternal blood

54
Q

What happes to a lot of glucose in the placenta?

A

Although the fetus receives a large amount of intact glucose, a lot of glucose is oxidised in the placenta into lactate, which is then used for fetal energy production

55
Q

Describe hepatic glucose production and develpment

A

Hepatic glycogenesis (glycogen syn.) and gluconeogenesis (glucose syn.) are thought to be triggered after birth, by stress hormones and by falling blood glucose levels

56
Q

What is seen towards birth in the liver?

A

Hepatic glycogen content and gluconeogenic enzymes increase towards term in the fetal liver

57
Q

Describe glucose transport over time;

A
  • As fetus grows, fetal metabolic demand increases so placental transport must increase.
  • More glucose is provided by the simultaneous decrease in fetal glucose concentration relative to that of the mother →↑transplacental glucose concentration gradient, producing the actual glucose supply to the fetus at point D - look at slides/graph for understanidng
58
Q

What mediates the increase in placental glucose transport?

A 
Transport increases for 2 reasons
–
efficiency of placenta
–
Fetal growth: decerase fetal glucose
59
Q

What is the function of lactate to the fetus;

A

Fetus can metabolise lactate aerobically with great efficiency; acts as a substrate reservoir.

  • Second must abundant substrate after glucose
60
Q

Describe fetal AA metabolism;

A
  • Primary source of AA is through umbilical uptake
  • Concentration of AA is higher in fetal plasma than maternal
    = Fetal growth requires net accretion of proteins
61
Q

Describe how pH influences AA uptake;

A

Mean umbilical venous arterial concentrations differences.
•
Acidic amino acids (taurine, aspartate, glutamate) show either no net flux or a negative (v-a) difference.
•
Neutral/basic amino acids demonstrate a large positive uptake by the fetus from the placenta.

62
Q

Describe the function of AA to the fetus;

A

•
The uptake of a.a. by the fetus exceeds their rate of accretion into tissue protein
•
Therefore, a.a. are available for oxidative metabolism

63
Q

Describe the role of fetal FFAs and ketoacids in metabolism;

A

Lipid metabolism in the fetus involves:

  • the incorporation of FFAs into membranes as phospholipids
  • deposition into adipose tissue
  • oxidation
64
Q

Can mammal fetuses synthesize lipids?

A

•
All mammalian fetuses studied so far have the capacity to synthesise lipids
•
Triglycerides, phospholipids, FFAs and volatile FAs are all found in the fetus

As gestational age increases fetal lipogenesis into adipose increases esp towards birth

65
Q

What may volatile FFA be used for?

A

In ruminants, the volatile fatty acid, acetate, contributes to fetal metabolism

Radioactive labelling of acetate to the fetus shows a wide range of compounds it is incorporated into including FFAs, steroids, and membrane lipids

Medsci 312 (28 decks)

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