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
The brain is a high energy demand organ. How does ketone use allow it to continue function?
Neurological manifestations of hypoglycaemia usually begin when glucose is <2.8mmol/L
In ketoacidosis, neurological manifestations are delayed and not typically seen until the serum glucose is much lower
How does the metabolic response to starvation differ to that of trauma in the following parameters
1) metabolic rate
2) body fuels
3) body protein
4) urinary nitrogen
5) weight loss
STARVATION
- low BMR
- body fuels and protein conserved
- Urinary nitrogen decreases
- slow weight loss
TRAUMA/DISEASE
- very high BMR
- body fuels and protein wasted
- very high urinary nitrogen
- rapid weight loss
Why is there a need for nutritional support in critical illness?
How is this done?
- catabolism exceeds anabolism
- carbohydrates are the preferred energy source and the fat mobilisation is impaired
Protein administeration to decrease breakdown of muscle protein
Why does lactic acidosis occur?
What is the commonest cause?
Impaired tissue oxygenation, leading to increased anaerobic metabolism
SEPSIS (commonest cause in hospitalised patients)
Other causes: hypovolaemia, HF, cardiopulmonary arrest
What are the 8 features of the hypermetabolic response to injury (trauma, surgery, critically ill)?
- increased BP and HR
- peripheral insulin resistance
- increased protein and lipid catabolism
- increased resting energy expenditure (BMR)
- increased body temperature
- total body protein loss
- muscle wasting
- acute phase protein response
Why is glucose raised in critical illness?
- stress mediators oppose anabolic actions of insulin (high catecholamines, cortisol)
- there is an enhancement on other energy substrates: adipose tissue lipolysis, skeletal muscle proteolysis, gluconeogenesis
- the suppressive effect of insulin on hepatic glucose release is weakened
What is the effect of high catecholamines in critical illness?
- enhance glycogen breakdown
- impair glucose disposal via alterations of the insulin-signalling pathway; and GLUT4 translocation in muscle and adipose tissue which results in peripheral insulin resistance
Why is there lean-muscle protein breakdown in critical illness?
- proinflammatory cytokines: TNF
- reduced ability to use lipids as energy
- skeletal muscle is major source of substrate for glucose production
How does protein catabolism effect the effects of insulin in critical illness?
Majority (75%) of whole body insulin-stimulated glucose uptake occurs in skeletal muscle
Muscle loss contributes to persistent insulin resistance
What is the role of catecholamines in the hypermetabolic response and cachexia?
Initiates adipose tissue browning
There is 10% loss in lean body mass during critical illness
State 5 effects of this
- increase risk of infection
- delays wound healing
- muscle weakness
- prolongs mechanical ventilatory utilisation
- inhibits cough reflexes
- delays mobilisation
- contributes to mortality
What are the endocrine complications of starvation that relate to the sex organs/hormones?
- suppression of hypothalamic-pitiutary-ovarian axis
- hypogonadotropic hypogonadism
- low GnRH, LH, FSH, estradiol
- Amenorrhoea, infertilty
- Leptin low (as a result of low fat mass)
- severe bone loss (osteopenia due to loss of collagen)
What are the endocrine complications of starvation that relate to the adrenal glands?
- increased hypothalamic-pituitary-adrenal activity: high cortisol (which causes breakdown of protein (muscle collagen) to glucose and urea
- this causes muscle weakness and osteopenia (osteopenia due to loss of collagen)
What are the endocrine complications of starvation that relate to the thyroid?
Sick euthyroid pattern
- low/normal TSH; low/normal T4; low T3
Caused by chronic undernutrition which decreases BMR
Therefore decreased conversion of T4 to T3
(which reduces metabolic rate)
