Metabolic And Endocrine Control During Special Circumstances Flashcards
Fuel sources
Normally available in the blood -
Glucose - Glucose is the preferred fuel source, Little (~12g) free glucose available, More glucose (~300g) stored as glycogen
Fatty acids - Can be used as fuel by most cells except red blood cells, brain and CNS, Stored as triacylglycerol (fat) in adipose, 10-15 kg fat in 70kg man (~2 months fuel supply)
Available under special conditions -
Amino acids - Some muscle protein (~6kg) can be broken down to provide amino acids for fuel source, Converted to glucose or ketone bodies, ~2 weeks supply of energy
Ketone bodies - Mainly from fatty acids, Used when glucose is critically short, Brain can metabolise instead of glucose
Lactate - Product of anaerobic metabolism in muscle, Liver can convert back to glucose (Cori cycle) or can be utilised as fuel source for TCA cycle in other tissues (e.g. heart)
Energy stores
Glycogen ~ 400g - Readily available source of glucose, Made & stored in liver and muscle
Made when glucose is in excess in blood
Fat ~10 -15kg Made from glucose and dietary fats when in excess, Stored as triacylglycerol in adipose tissue Source of: fatty acids and glycerol
Muscle protein ~6kg available
Used in emergency
Amino acids can be: Glucogenic (e.g. Ala & Val), Ketogenic (Lys & Leu) or both (e.g. Tyr & Phe)
Store ‘filled’ by normal growth and repair processes
Food is consumed episodically leading to intermittent supply
Absorbed nutrients are sometimes available in excess and sometimes unavailable (feed/fasting cycle, starvation)
Body needs to be able to draw upon long and short term energy stores
Hormones and metabolic control
Anabolic hormones - Promote fuel storage (using Insulin and Growth Hormone (which increases proteins synthesis)) - If there is a lack of insulin then body enters a catabolic state
Catabolic hormones - promote release form stores and utilisation - e.g. Adrenaline, Cortisol, Growth hormone (which can increase lipolysis & gluconeogenesis) and Thyroid hormones (hence with overactive thyroid - you lose weight)
The feeding fasting cycle
Effects of feeding - Increase in blood glucose stimulates pancreas to release insulin
Increases glucose uptake and utilisation by muscle and adipose (GLUT 4)
Promotes storage of glucose as glycogen in liver and muscle.
Promotes amino acid uptake and protein synthesis in liver and muscle.
Promotes lipogenesis and storage of fatty acids as triacylglycerols in adipose tissue.
Effects of fasting - Blood glucose falls & insulin secretion depressed.
Reduces uptake of glucose by adipose and muscle.
Low blood glucose stimulates glucagon which stimulates -
Glycogenolysis in the liver to maintain blood glucose for brain and other glucose dependent tissues
Lipolysis in adipose tissue to provide fatty acids for use by tissues
Gluconeogenesis in the liver to maintain blood glucose for brain and other glucose dependent tissues
Energy starvation
Reduction of blood glucose stimulates release of cortisol from adrenal cortex & glucagon from pancreas.
Stimulate gluconeogenesis & breakdown of protein & fat.
Reduction in insulin & anti-insulin effects of cortisol prevent most cells from using glucose & fatty acids are preferentially metabolised.
Glycerol from fat provides important substrate for gluconeogenesis, reducing the need for breakdown of proteins.
Liver starts to produce ketone bodies & brain starts to utilise these sparing glucose requirement from protein
Kidneys begin to contribute to gluconeogenesis
Once fat stores depleted system must revert to use of protein as fuel
Death usually related to loss of muscle mass (respiratory muscle: infection).
Metabolic and endocrine adaptations to pregnancy
There is a Number of alterations to maternal metabolism and endocrine system
As theres a a need to accommodate increased demands of developing fetus and placenta
Growth of fetus requires lots of energy & raw materials
2/3rds of fetal growth occurs over the last 1/3 of pregnancy
From 28 weeks onwards fetus grows from ~1000g to ~3500g
Two main phases of metabolic adaptation during pregnancy
In early pregnancy, mother is in an anabolic state
Increase in maternal fat stores
Small increase in level of insulin sensitivity.
Nutrients are stored to meet future demands of rapid fetal growth in late gestation and lactation after birth.
Late pregnancy characterised as catabolic state - decreased insulin sensitivity (increased resistance)
Increase in insulin resistance results in maternal glucose and free fatty acid concentration
Allows for greater substrate availability at the placenta, therefore benefiting fetal growth.
Placental transfer - Most substances transfer by simple diffusion down concentration gradients (some active transport e.g. amino acid transporters)
Glucose is principal fuel for fetus and transfer facilitated by transporters (mainly GLUT 1).
The “Aggressive parasite” - Fetus controls maternal metabolism to ensure its own survival
The placenta, fetal adrenal glands and fetal liver, constitute a new endocrine entity, known as the fetoplacental unit
Placenta secretes a wide range of proteins that can control the maternal Hypothalamic pituitary axis to help favour nutrient exchange at the placenta for the baby
Important placental steroid hormones include oestriol and progesterone
Maternal metabolic changes during pregnancy
Maternal metabolic changes during first half of pregnancy
Changes to maternal metabolism during first 20 weeks of pregnancy related to a preparatory increase in maternal nutrient stores (mainly adipose tissue).
In preparation for:
Rapid growth rate of fetus
Birth
Subsequent lactation
Increasing levels of insulin (
Anti - insulin hormones
Placenta secretes several hormones that exert an anti-insulin effect on maternal metabolism
Tend to result in transient hyperglycaemia after meals because of increased insulin resistance
Overall late pregnancy has blood glucose ~10% lower since insulin levels are ~1.65 x higher in fasting state and ~ 3 x higher in postprandial state.
Hypoglycaemia can occur between meals and at night because of the continuous fetal draw of glucose
Insulin secretion in pregnancy - Increased appetite in pregnancy means more glucose is ingested
Oestrogens and progesterone increase sensitivity of maternal pancreatic
Gestational diabetes
Clinical implications
Affects 3–10% of pregnancies
Increased incidence of miscarriage
Incidence of congenital malformation 4x higher
Fetal macrosomia
Disproportionate amount of adipose around shoulders and chest could lead to shoulder dystocia (Shoulders get “stuck” during birth)
Associated with hypertensive disorders of pregnancy such as Gestational hypertension and Preeclampsia
Risk of complications greatly reduced if gestational diabetes is diagnosed and managed
Risk factors - Maternal age >25 years, Body mass index >25 kg/m2, Race/Ethnicity (More common in Asian, Black and Hispanic ethnic groups), Personal or family history of Diabetes and Family history of macrosomia
Management - Initial dietary modification including calorific reduction in obese patients
Insulin injection if persistent hyperglycaemia is present:
(7.5-8 mmol/l postprandial or >5.5-6 mmol/L fasting)
Regular ultrasound scans to assess fetal growth & well being
Metabolic response to exercise
The switch from rest to exercise involves rapid adaptations in a range of systems -
Musculo-skeletal system - Cardiovascular system - Respiratory system - Temperature regulation
The metabolic response needs to ensure -
Increased energy demands of skeletal and cardiac muscle are met by mobilisation of energy stores.
Minimal disturbances to metabolic homeostasis by keeping rate of mobilisation equal to rate of utilisation. Glucose supply to brain is maintained. End products of metabolism are removed as quickly as possible.
Magnitude and nature of response depends on -
Type of exercise (muscles used), Intensity and duration of exercise and Physical condition and nutritional state of individual
Energy requirements of exercise - ATP
Muscle glycogen
Additional intensive exercise (anaerobic) for up to ~2 minutes can be sustained by breakdown of muscle glycogen
If exercise is low intensity enough O2 can be supplied for complete oxidation of glucose and glycogen stores (from muscle + liver) could theoretically last for ~60 minutes (e.g. jogging)
Blood glucose
Liver is principal organ for regulating blood glucose
Exercise results in an increase in hepatic blood glucose production through glycogenolysis and gluconeogenesis
Liver recycles lactate produced by anaerobic metabolism (Cori cycle).
Muscle takes up blood glucose via GLUT4 transporter (insulin promotes translocation to plasma membrane) and GLUT1 (constitutively active)
Exercising muscle also has insulin independent process of glucose uptake (
Fatty acids as fuel
Major store of triacylglycerol in adipose (~15kg) but also some in muscle itself
Theoretically could provide enough energy for ~48 hours of low intensity exercise
Can only be used in aerobic conditions due to -
Slow release from adipose tissue
Limited carrying capacity in blood
Capacity limited by uptake across mitochondrial membrane (carnitine shuttle)
You get a low rate of ATP production but a high capacity for sustained production
Energy sources during different exercises
Short, high intensity exercise
Cannot deliver sufficient oxygen to muscles in time
Once high energy phosphate stores used (~5 sec) must create ATP anaerobically - Inefficient - Incomplete metabolism of glucose
Produces lactate (lactic acid) with subsequent build up in H+ produces fatigue
Cannot deliver extra glucose to muscle cells fast enough
Need muscle store of glycogen
Helps to spare blood glucose for brain
1500m middle distance - Medium intensity
Can deliver some extra oxygen to muscles
However, still ~40% anaerobic metabolism
Aerobic metabolism can use fatty acids as well as glucose
Three phases to race:
Initial start uses creatine phosphate and anaerobic glycogen metabolism.
Long middle phase in which ATP is produced aerobically from muscle glycogen (relies on adequate supply of O2 to muscles).
Final finishing sprint relies again on the anaerobic metabolism of glycogen and produces lactate.
Marathon - Low intensity, long duration - 95% aerobic
Use of - Muscle glycogen, Liver glycogen and Fatty acids
Muscle glycogen depleted in a few minutes. Glucose from liver glycogen peaks at ~1 hour then declines steadily
Utilisation of fatty acids rises steadily from 20-30 minutes
Hormonal control of the metabolic response to prolonged excercise
Over the course of running a marathon:
Insulin levels fall slowly (inhibition of secretion by adrenaline)
Glucagon levels rise: Stimulates glycogenolysis (activates glycogen phosphorylase) Stimulates gluconeogenesis (PEPCK & fructose 1,6 bisphosphatase) Stimulate lipolysis (Hormone sensitive lipase)
Adrenaline and growth hormone rise rapidly
Adrenaline stimulates glycogenolysis & lipolysis
Growth hormone stimulates lipolysis & gluconeogenesis
Cortisol rises slowly
Stimulates lipolysis & gluconeogenesis
