S11 L2 - Metabolic and endocrine control during special circumstances and disorders Flashcards
- *Fuel sources**
- Normally available in blood
- Avialable under specificial conditions
- *Energy stores**
- 3
Normally available in 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 specifical conditions:
Amino acids:
• Some muscle protein (~6kg) can be broken down to provide amino acids for fuel
• 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:
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- *Key features of metabolic control**
- Timeline of getting energy…
- Which hormones are anabolic hormones, which hormones are catabolic?
- Timeline of getting energy…
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- *Hormones and metabolic control**
- Anabolic hormones
- Catabolic hormones
Role of insulin
Hormones and metabolic control
- Anabolic hormones
- Catabolic hormones
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Role of insulin:
Stop:
• Gluconeogenesis
• Glycogenolysis
• Lipolysis
• Ketogenesis
• Proteolysis
Go:
• Glucose uptake in muscle and adipose (GLUT 4)
• Glycolysis
• Glycogen synthesis
• Protein synthesis
- *The feeding fasting cycle**
- Effects of feeding
- Effects of fasting
The feeding fasting cycle:
- Effects of feeding
- Effects of fasting
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Energy starvation
Refeeding syndrome - why must increasing protein content of diet be gradual?
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).
- *Refeeding syndrome:**
- Hypophophataemia
- Hyperammonia
- *Metabolic and endocrine Adaptions to Pregnancy**
- Why must this adaptions occur?
- What is the average mother net gain during pregnancy?
- When does fetus growth mostly occur during pregnancy?
- *How do substances transfer over the placenta?
- ** Other substances
- Glucose
Metabolic and endocrine Adaptions to Pregnancy
- Why must this adaptions occur?
To accomodate the increasing demands of developing fetus and placenta
What is the average mother net gain during pregnancy?
8kg
When does fetus growth mostly occur during pregnancy?
2/3rd of fetal growth occurs over last 1/3 of pregnancy
How do substances transfer over the placenta?
Placental transfer
Most substances transfer by simple diffusion down concentration gradients (some active transport e.g. amino acids transporters)
Glucose is principal fuel for fetus and transfer fascilitated diffusion by GLUT1
- *Two main phases of metabolic adaption during pregnancy, and explain briefly:**
1. _____
2. _____ - *1. Anobolic phase**
- When is this?
- What happens?
- Why?
- *Two main phases of metabolic adaption during pregnancy, and explain briefly:**
1. Anabolic phase - Preparatoy increase in maternal nutrient stores (espcially adipose)
2. Catabolic phase - Maternal metabolism adapts to meet an increasing demand by fetal-placental unit - *1. Anobolic phase: First 20 weeks**
- Increase in maternal fat stores
- -> Nutrients are stored to meet future demands of rapid growth in late gestation, birth and lactation after birth
- Increasing levels of insulin (high insulin: anti-insulin ratio) promote anabolic state in mother
- *2. Catabolic phase**
- Changes that occur (at least 3)
- What these changes means…
- *Anti-insulin hormone**
- Produced by…
- Names of 2 examples…
- Effect on mother…
- What can happen to maternal glucose between meals and at night?
- Late pregnancy characterised as catabolic state
- *- Concentration of nutrients in the maternal circulation kept relatively high by:**
- Reducing maternal utilisation of glucose by switching tissues to use of fatty acids (so glucose can be used by the fetus)
- Delaying maternal disposal of nutrients after meals
- Releasing fatty acids from stores built up during 1st half of pregnancy
- Decreased insulin sensitivity (increased insulin resistance) -> Increases maternal glucose and free fatty acid concentration -> Allows for greater substrate availability for fetal growth. This is achieved by: production of anti-insulin hormones by fetal-placental unit
Anti-insulin hormones:
Placenta secretes several hormones that exert an anti-insulin effect on maternal metabolism:
- Corticotropin releasing hormone (CRH)
- Progesterone
Result in transient hyperglycaemia after meals because of insulin resistance
What can happen to maternal glucose between meals and at night?
Hypoglycaemia can occur between meals and at night because of the continuous fetal draw of glucose
- *Insulin secretion in pregnancy - general**
- What happens to the beta cells in the pancreas
- Why?
- Which hormones cause this?
- Why may gestational diabetes occur?
Increased appetite in pregnancy means more glucose is ingested
• Oestrogens and progesterone increase sensitivity of maternal pancreatic β-cells to blood glucose
- β-cell Hyperplasia (more cells)
- β-cell Hypertrophy (bigger cells)
• Leads to increased insulin synthesis & secretion
• If β-cells do not respond normally, blood glucose may become seriously elevated & Gestational diabetes may develop
- *Gestational diabetes**
- Background to why this occurs
- Causes
- Which women are more at risk of developing it?
- Risk factors for foetus
- Risk factors for mum
- Management
Gestational diabetes
Background to why this occurs: Increase appetite, increase food intake, increased glucose ingested. Oestrogen and progesterone help to increase sensitivity of maternal pancreatic beta-cells to blood cells. They do this through: beta-cell hypertrophy and beta-cell hyperplasia. This leads to increased insulin synthesis and secretion.
Problem occurs when: the beta-cells in the maternal pancreas do not respond normally, leads to hyperglycaemia (Gestational diabetes).
Causes:
1. Autoimmune (like type 1 DM)
2. Genetic susceptibility similar to maturity onset diabetes
3. Beta-cell dysfunctional in the setting of obesity and chronic insulin resistance (like type 2 DM) – this is most common
Which women are more at risk of getting it:
- BMI greater than 25kg/m2
-Maternal age 25+
- Race/ethnicity – more common in Asian, Black, Hispanic
- Personal or family history of diabetes
- Family history of macrosomia
Risk factors for foetus:
- Congenital malformation 4x higher
- Miscarriage risk
- Macrosomia (big baby)
- Shoulder dystocia
Risk factors for mum:
- Preeclampsia (High BP, this then causes protein in urine)
- Gestational hypertension
- Development of Type 2 diabetes mellitus later in life
Management: Depends the cause. Dietary modification (caloric reduction) in obese patients. Insulin injections. Regular ultrasound scans to assess fetal growth and well-being
- *Metabolic response to exercise**
- Metabolic response needs to ensure
- Magnitude and nature of response depends on…
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
• Physical condition and nutritional state of individual
- *Energy requirements of exercise: Order…**
1. ATP stores - how long do they last, synthesis…
2. Creatine phosphate
Beyond initial burst of energy…
1. ATP stores:
• ATP “stores” in muscle are limited (~5 mmol/kg)
• In theory enough to last ~2 seconds during a sprint
• ATP must therefore be rapidly resynthesised at a rate that meets the metabolic demands placed upon cell
• Depending on rate of ATP hydrolysis, cell will employ different metabolic strategies to match re-synthesis rate with hydrolysis rate
ATP -> ADP + Pi + energy
2. Creatine phosphate:
Muscle creatine phosphate stores (~17mmol/kg muscle) can rapidly replenish ATP to provide immediate energy
• Still only enough for ~5 seconds worth of energy during a 100m sprint
Creatine phosphate —creatine kinase—> creatine
- *Beyond initial burst of energy… further ATP must be supplied by:**
- Glycolysis
- Oxidative phosphorylation
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**
- Cori-cycle
Fatty acids as fuel
- *Fuel usage in:**
- 100m sprint
- 1500m middle distance
- Marathon
- Hormonal control of metabolic response to prolonged exercise
- 100m sprint:
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
• 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
Benefits to exericse
