The effects of pregnancy and exercise on metabolism Flashcards
Describe the metabolic and hormonal response to pregnancy
The metabolism of all major maternal nutrients are affected during pregnancy - the magnitude of the effect depending on the stage of pregnancy.
These changes are long-term adaptive responses to maternal metabolism that are hormonally mediated
Why is the environment in which the foetus develops controlled by the maternal metabolism?
The rate of transfer of nutrients across the placenta to the foetus is dependent on their concentration in the maternal circulation
Why does maternal metabolism need to change as pregnancy proceeds?
So:
- The foetus is supplied with the range of nutrients it requires
- Nutrients are supplied at the appropriate rate for each stage of development
- Minimal disturbances to maternal nutrient homeostasis
- Foetus is buffered from any major disturbances in maternal nutrient supply
What maternal hormones are involved in the long-term adaptive responses of maternal metabolism?
Insulin
What hormones produced by the foetal-placental unit are involved in the long-term adaptive responses of maternal metabolism?
Corticotropin releasing hormone (CRH) Oestrogen Progesterone Placental lactogen etc...
What is the role of maternal insulin in controlling changes to maternal metabolism during pregnancy?
Its concentration in the maternal circulation increases as pregnancy proceeds and it acts to promote the uptake and storage of nutrients, largely as fat in maternal adipose tissue
Placental hormones become increasingly important as pregnancy proceeds. They have a number of effects on maternal metabolism. In general what do these effects largely achieve?
Anti-insulin effects - impaired glucose uptake in maternal adipose and muscle
What are the general metabolic changes to maternal nutrient homoeostasis during the first 20 weeks of pregnancy?
Increasing insulin:anti-insulin ratio increases maternal nutrient stores in preparation for the more rapid growth of the foetus, birth and subsequent lactation
What is the second half of pregnancy characterised by?
A marked increase in the growth of placenta and foetus
The demands of the foetal-placental unit for nutrients in the second half of pregnancy are met by keeping the concentration of nutrients in the maternal circulation relatively high. How is this achieved?
- Reducing the maternal utilisation of glucose by switching tissues to the use of fatty acids
- Delaying the disposal of maternal nutrients after a meal
- Releasing fatty acids from the stores built up during the first half of pregnancy
How is the concentration of nutrients in the maternal circulation raised in the second half of pregnancy?
Maternal insulin increases to rise but this is met by an even faster rate of increase in foetal-placental unit anti-insulin hormones, which produces a decrease in the insulin:anti-insulin ratio
Why are more ketone bodies produced in the maternal liver in the second half of pregnancy?
Due to the reduced insulin: anti-insulin ratio and greater availability of fatty acids (mobilisation of maternal adipose tissue) to the liver, ketone body production is switched on in the maternal liver
What use is there of the extra ketone bodies during pregnancy?
Used as fuel by developing foetal brain
Both basal and stimulated insulin production normally increases throughout pregnancy. How is this extra demand met by the pancreatic beta cells?
Beta-cell hyperplasia
Beta-cell hypertrophy
Rate of insulin synthesis in beta-cells increases
Why does gestational diabetes occur?
Endocrine pancreas is unable to meet the extra demands of pregnancy and the pancreas fails to release the increased amounts of insulin required. Consequently there is a loss of control of metabolism, blood glucose levels rise and diabetes results
What happens to women who have gestational diabetes after they have given birth?
Increased metabolic demands of pregnancy removed
Hormone levels change
Endocrine pancreas can now respond sufficiently
Diabetes disappears.
Women who have gestational diabetes are at a higher risk of what, compared to women who didn’t develop it?
Type 2 diabetes
Why are some women high risk for gestational diabetes?
They have a high baseline of insulin resistance. Insulin resistance increases during pregnancy and so a high baseline can result in it increasing over the threshold where diabetic symptoms occur
In general, what does the body need to do during exercise?
- Meet the acute oxygen and fuel demands of cardiac and skeletal muscle
- Remove end-products of metabolism
What does the metabolic response to exercise need to ensure?
- Increased demands of skeletal and cardiac muscle are met by mobilisation of fuel molecules from energy stores
- Minimal disturbances to homeostasis by keeping the rate of mobilisation equal to the rate of utilisation
- Glucose supply to the brain is preserved (prevent hypoglycaemia)
- End products of metabolism are removed as quickly as possible
What is the magnitude and nature of the metabolic response dependent on?
- Type of exercise (muscles used)
- Intensity and duration of exercise
- Physical condition and nutritional status of the individual
Under high intensity activities of short duration (e.g. 100m sprint) what conditions does the skeletal muscle have to work under?
Anaerobic conditions as the supply of oxygen to muscle is inadequate to maintain aerobic metabolism
Under low intensity activities of longer duration (e.g. marathon), what conditions does the skeletal muscle work under?
The supply of oxygen to muscles is adequate to allow aerobic metabolism
The increased energy requirements of exercise chiefly reflect the increased activity of which muscle(s)?
Skeletal and cardiac muscles (increased activity of respiratory muscle is less significant)
The ATP present in muscle in theory would be used up very quickly in a 100m sprint (approximately 2 seconds!) but it does not fall below 20% because it is regenerated by a variety of mechanisms.
(i) How is ATP initially regenerated in muscle?
(ii) What fuel is used next to replenish ATP?
(i) Creatine phosphate
(ii) Muscle glycogen
During medium duration medium intensity exercise (1500m) the body regenerates ATP using a mixture of aerobic (60%ish) and anaerobic (40%ish) metabolism of glycogen. What types of metabolism occur in these three stages of the race?
- Initial sprint
- Long middle phase
- Final finishing burst
- Uses muscle ATP, creatine phosphate and anaerobic glycogen metabolism
- ATP produce aerobically from glycogen - relies on adequate supply of oxygen to muscles
- Anaerobic metabolism of glycogen, producing lactate
During a marathon the carbohydrate stores in the body are insufficient to meet the energy requirements of muscle cells, what do they start to oxidise instead?
Fatty acids
What are the major features of the metabolic response to long duration exercise?
- Muscles work aerobically (supply of oxygen increased by cardiovascular response) and can use all types of fuel molecules not just glucose
- The origin and type of fuel changes as exercise proceeds
What is the major fuel used during the initial phase of marathon running?
Muscle glyocgen
How do many marathon runners try to prolong their utilisation of glycogen?
By eating carbohydrate rich diets to increase their glycogen stores. This is most effective after exercise as exercise promotes the storage of glucose as muscle glycogen rather than its conversion to lipid
As a marathon proceeds and muscle glycogen stores are used up, the use of what fuel molecule in circulation increases?
Blood glucose. Blood glucose concentration remains relatively stable however as it is replaced by the liver’s limited glycogen stores and from gluconeogenesis
Why does exhaustion occur?
When gluconeogenesis used up the limited substrates available and blood glucose levels fall
The utilisation of what fuel source gradually increase with time during a marathon?
Fatty acids. They can be used as the muscle cells are under aerobic conditions.
What is the chemical reaction of ATP hydrolysis?
ATP + H2O –> ADP + Pi + energy
How is ATP regenerated from creatine phosphate?
creatine phosphate + ADP –> ATP + creatine
What is the major tissue story of energy that can be called upon during exercise?
- glycogen - muscles and liver
2. Triacyglycerols - adipose tissue and small amount in muscle cells
What is the major circulating fuel molecules that can be called upon during exercise?
Glucose
Free fatty acids
Why can muscle glycogen stores last for 60min of low intensity exercise but only 2 minutes of high intensity exercise?
Low intensity exercise has a lower ATP consumption than high intensity.
Low intensity exercise uses aerobic respiration which yields more ATP per mole of glycogen than anaerobic respiration in high intensity exercise (which produces lactic acid)
What is the liver store of glycogen used for?
To prevent hypoglycaemia and the associated impairment of CNS function
What are the advantages of using muscle glycogen over circulating glucose?
- Availability not affected by blood supply
- No need for membrane transport into muscle cells
- Produced G-6-P without using ATP (glycogen phosphorylase uses Pi)
- Mobilisation can be very rapid
Why can mobilisation of glycogen be rapid?
- Highly branched structure of glycogen allows many sites for enzyme attack
- Glycogen phoshorylase activity can be changed rapidly by covalent modification (phosphorylation) and allosteric activation (ADP and Ca2+)
A serious problem that limits anaerobic metabolism of glucose from muscle (from glycogen or circulating glucose) is the build-up of lactate and H+. By which mechanisms does H+ impair muscle function?
When H+ exceeds the buffering capacity of the muscle cells it impairs their function and leads to fatigue by:
- Inhibition of glycolysis
- H+ interferes with actin/myosin interaction
- H+ causes sarcoplasmic reticulum to bind calcium (inhibits contraction)
What are the factors that limit the use of fatty acids by muscle?
- Rate of FA release from adipose tissue
- Limited capacity of blood to transport FAs-req. albumin
- Rate of FA uptake by M.cells and M. mitochondria
- FA ox. requires more O2/mole of ATP produced than glucose
- FAs can only be metabolised under aerobic conditions
What controls the metabolic response during high intensity exercise?
NS - noradrenaline
some endocrine input - adrenaline
Why does endurance not matter during short duration high intensity exercise?
The duration is so short that not enough H+ builds up from anaerobic respiration, to produce fatigue
In medium duration medium intensity exercise, why is H+ not a problem?
The amount produced can be buffered by muscle. So the body needs to get rid of a large amount of CO2 but is not affected by high concentrations of H+ and therefore fatigue
How are the metabolic changes observed during long duration low intensity exercise controlled?
- Largely hormonal (insulin, adrenaline, growth hormone, glucagon and cortisol)
- Some input from NS (noradrenaline)
What happens to insulin levels during a marathon?
Fall progressively due to inhibition of insulin secretion by adrenaline and noradreanline
What happens to adrenaline, noradrenaline and growth factor levels during a marathon?
Increase rapidly
What happens to glucagon and cortisol levels during a marathon?
Increase gradually
The net effect of the hormonal and neurotransmitter changes during exercise is a progressive fall in the insulin: anti-insulin ratio. What effects does this have?
- Increases glycogenolysis in the liver
- Increases gluconeogenesis in the liver
- Increases lipolysis in adipose tissue
- NO EFFECT on ketogenesis in liver (insulin still present)
Define fatigue
The inability to maintain a given power output affecting the intensity and/or duration of exercise.
There are a number of causes of fatigue both psychological and biochemical.
What are the biochemical causes of fatigue?
- Depletion of muscle glycogen
- Accumulation of H+ in muscle
- Dehydration - reduced capacity for sweating, reduces heat loss, increases body temperature
Which whole body responses to prolonged exercise can be affected by training?
- Increased fuel consumption by muscles - need to be supplied with fuels
- Increased delivery of O2 to muscles - vasodilation of arterioles
- Increased cardiac output - beats faster, larger stroke volume
What changes to the CVS occur in response to prolonged exercise?
- Vasodilation of arterioles - increased delivery of oxygen to muscles
- Increased cardiac ouput - beats faster, larger stroke volume
- Redistribution of blood flow away from gut, kidneys to muscles
What changes to muscle cells occur in response to prolonged exercise?
- Increased fuel consumption by muscles
- Increased ATP production and utilisation by muscles (approximately 20% efficiency)
- Increased removal of CO2, H+ and lactate from muscles
What thermoregulation occurs during prolonged exercise?
Increased heat productions is dissipated by sweating
How is the respiratory system affected during prolonged exercise?
Changes to breathing - increases in rate and depth
What is the general effect of training on the body?
It creates long term adaptations to improve capacity for physical work (stamina).
The long term adaptations that occur due to training largely affect which body systems?
cardiovascular and musculoskeletal systems with minimal changes to respiratory systems. All are readily reversible
What cardiovascular changes occur due to training?
- More 2,3-bisphosphoglycerate in blood (lowers affinity of haemoglobin for oxygen)
- Heart beats slower for same cardiac output
What is increased in skeletal muscle due to changes occurring from training?
- GLUT4 glucose transport proteins in cell membrane
- Storage of glycogen
- Potential for oxidative metabolism, especially fatty acids - more mitochondria and more oxidative enzymes in mitochondria
- Number and size of muscle fibres
- Vascularisation (capillary density) of muscles - improves O2 supply
- Myoglobin content of muscle (ability to store O2 in muscle)
What are the benefits of exercise?
- Body composition changes (decreased adipose, increased muscle)
- Glucose tolerance improves (muscle glycogenesis increases)
- Insulin sensitivity of tissues increases
- Blood TAGs decrease (decreased VLDL&LDL and increased HDL)
- Blood pressure falls
- Psychological effects - feeling of “well-being”
What are the benefits of exercise for diabetics?
- Body composition changes (decreased adipose, increased muscle)
- Glucose tolerance improves (muscle glycogenesis increases)
- Insulin sensitivity of tissues increases
- Blood TAGs decrease (decreased VLDL&LDL and increased HDL)
- Blood pressure falls
The fibres of skeletal muscle vary widely in both their physical properties (e.g. speed of contraction) and metabolic properties (e.g. oxidative capacity). Which two major types of fibre can be distinguished histologically?
Type i (red) and Type II (white)
Which type of muscle fibres do long-distance runners have over 70% of?
Type I
Which type of muscle fibres do sprinters have over 70% of?
Type II
Red muscle fibres (type I) are used for low intensity, high endurance exercise. List some of their properties
Slow speed of contraction Slow speed of fatigue Good capillary supply Many mitochondria High oxidative capacity Low glycolytic capacity High FA oxidation capacity High myoglobin content
White muscle fibres (type II) are used for high intensity, low endurance exercise. List some of their properties
Fast speed of contraction Fast speed of fatigue Moderate/poor capillary supply Few mitochondria Moderate/low ocidative capacity High/moderate glycolytic capacity Low FA oxidation capacity Low myoglobin content
