Metabolic response to starvation vs injury, sepsis Flashcards
How does simple starvation differ to catabolic weight loss?
In simple starvation
- metabolic adaptation
- lean tissue conserved
In catabolic weight loss
- no adaptation
- lean tissue breakdown continues despite nutrient intake
Describe simple starvation by considering the following metabolic activity
- basal metabolic rate
- glucose levels
- glucose utilisations
- gluconeogenesis
- protein catabolism
- fat catabolism
- ketone utilisation
- ketosis
- ketosuria
- decreased basal metabolic rate (BMR)
- low glucose levels
- limited glucose use
- increase gluconeogenesis initially, decrease after 5-7 days
- low protein catabolism
- high fat catabolism
- increase ketone use
- ketosis present
- ketosuria present
Describe starvation superimposed on to injury or stress by considering the following metabolic activity
- basal metabolic rate
- glucose levels
- glucose utilisations
- gluconeogenesis
- protein catabolism
- fat catabolism
- ketone utilisation
- ketosis
- ketosuria
- decreased or normal BMR initially
- high glucose levels
- increased glucose use
- increased gluconeogenesis
- high protein catabolism
- low/no fat catabolism
- decreased ketone use
- no ketosis or ketosuria
Patients with anorexia nervosa have a nutritional deficiency, severe restriction of nutritional intake despite having a low body weight.
This results in low glucose. How does the body respond to this?
Think about the energy supply
Starvation ketosis
- Which is a physiological response for alternative energy supply
Brain requires some glucose for energy but adapts to using ketones which can cross BBB
Glucose above 2.2.mmol/L is maintained to support RBCs which do not have mitochondria and require glucose for energy, at the expense of protein
Muscles also adapt to ketones
Low glucose causes a decline in insulin which inhibits further glucose uptake and promotes ketone use
Why might urea be raised in a patient with anorexia nervosa?
High serum urea indicates protein (muscle) breakdown and/or AKI
How is ketosis promoted in anorexia nervosa?
- low glucose causes a decline in insulin which inhibits further glucose uptake and promotes ketone use
- high glucagon activates hormone sensitive lipase
This causes breakdown of TG to FFA
Survival time in anorexia nervosa depends on fat stores. Once these are depleted what happens?
Depletion of protein
Protein degradation accelerates just before death
- Death occurs from loss of heart, liver or kidney function
State three causes of ketoacidosis
- DIABETES (glucose is high but cannot be utilised so ketones provide alternate energy supply)
- Fasting ketosis
- Alcoholic ketoacidosis: hyperketonaemia and metabolic acidosis without significant hyperglycaemia
Why does ketoacidosis occur in the context of alcoholism?
Ethanol metabolised to acetic acid (ketone)
NA and cortisol amplify fasting lipolysis (Trigs-FFA-ketones)
Especially in malnourished
Outline the pathogenesis of ketoacidosis
Liver produce ketones under stimulation by low insulin and high glucagon levels
(secondary to fasting state, low carb diet, DM)
Lipase is activated which causes the breakdown of fat stores (TGs–> long chain fatty acids and glycerol)
Fatty acids transported to liver
Fatty acids enter mitochondria and are oxidised to acetyl-CoA
Either enter
(1) Krebs cycle and generate ATP
(2) Generate ketones (Acetone, acteoacetate, bet-hydroxybutyrate), FFA, cholesterol
During prolonged starvation, fasting (DM) oxaloacetate is depeleted in liver due to gluconeogenesis which impedes the first pathway
When does ketosis take place?
How does early ketosis differ to late ketosis?
Ketone production by the liver is a physiological response to fasting
Mild ketosis occurs after 12 hours of fasting
- approx 1mmol/L
After 20 days
- 8-10 mmol/L
Serum bicarbonate falls by 7-8 mmol/L
What determines the rate of ketone synthesis in a fasting state?
The amount of utilisation by brain, muscle, kidney
How does stabilisation of fasting ketosis take place?
- Stimulation insulin release, despite low glucose
- Increased sensitivity of adipose tissue to insulin inhibitory effect on fatty acid release
- Direct inhibition of lipolysis by ketones
Long term effects of fasting ketosis?
No adverse effects with fasting ketosis
What is a ketone?
A water soluble, fat derived molecule used for fuel, particularly when glucose is low
