Metabolic response to starvation vs injury, sepsis Flashcards
simple starvation vs injury, sepsis
Simple starvation - metabolic adaptation, lean tissue conserved
Catabolic weight loss - no adaptation, lean tissue breakdown continues despite nutrient intake
Features of simple starvation
- Decreased BMR
- Low glucose levels
- Increase gluconeogenesis initially, decrease after 5-7 days
- Protein catabolism low
- High fat catabolism
- Increased ketone use
- Ketosis present
- Ketosuria present
Features of starvation superimposed on to injury or stress
- Decreased or normal BMR initially
- High glucose levels
- Increased gluconeogenesis
- High protein catabolism
- Low/none fat catabolism
- Decreased ketone use
- Ketosis absent
- Ketosuria absent
Starvation - anorexia nervosa
- Nutritional deficiency, severe
- Severe restriction of nutritional intake - despite extremely low body weight
- Glucose - low
- Starvation ketosis
- Physiological response for alternative energy supply
Case - starvation - 17 y female, depressed, stopped eating, lost weight and was weak
- Glucose maintained > 2.2 mmol/L at expense of protein to provide energy for RBCs which do not have mitochondria and require glucose for energy
- Brain requires some glucose for energy, but adapts to using ketones as can cross blood-brain barrier
- In liver FFA for energy and conversion to ketones
- Low glucose causes decline in insulin and increase in glucagon release resulting in degradation: glycogen, fat stores, protein
- To maintain glucose supply to cells without mitochondria: RBCs brain requires some glucose
- Brain adapts further to ketones for energy
- Muscles adapt to ketones and spare further protein breakdown
- Low insulin does not allow glucose uptake, ketones used
- High glucagon activate hormone sensitive lipase, breakdown of TG to FFA (Fat tissue)
What do low glucose levels result in
- Low glucose causes decline in insulin and increase in glucagon release
- Resulting in degradation: glycogen, fat stores, protein
What might serum analysis show in starvation
- Increased urea, ketones
- High urea indicates protein(muscle) breakdown and or AKI
- Ketones indicate use of an alternative energy supply from TG-FFA breakdown
Starvation case - treatment and prognosis
Rx: psychotherapy, antidepressants, diet 1800 cal
Survival time depends on fat stores
After depletion of fat stores
Only source energy is protein
Protein degradation accelerates
Death from loss of heart, liver or kidney function
Normal glucose metabolism
- Postprandial increase blood glucose
- Stimulates insulin release
- Insulin mediates glucose uptake into skeletal muscle, fat tissue
- Suppresses hepatic gluconeogenesis
Most common cause of ketoacidosis
Diabetes
Why does ketoacidosis occur in diabetes
The absence of insulin also leads to the release of free fatty acids from adipose tissue (lipolysis), which are converted through a process called beta oxidation, again in the liver, into ketone bodies (acetoacetate and β-hydroxybutyrate).
β-Hydroxybutyrate can serve as an energy source in the absence of insulin-mediated glucose delivery, and is a protective mechanism in case of starvation.
The ketone bodies, however, have a low pKa and therefore turn the blood acidic (metabolic acidosis)
Ketoacidosis
Glucose high, but cannot be utilised
Ketones alternative energy supply
Fasting ketosis
Alcoholic ketoacidosis
Alcoholic ketoacidosis; characterized by
hyperketonemia and metabolic acidosis without significant hyperglycemia
Especially if malnourished
Ethanol metabolised to acetic acid(ketone)
Noradrenaline & cortisol amplify fasting lipolysis (Trigs-FFA-ketones)
What is ketoacidosis stimulated by
- Liver production of ketones
- Stimulated by low insulin and high glucagon
- Secondary to low glucose - fasting, low carbohydrate diet, diabetes
- Lipase activated
- Fat stores - triglycerides - long chain fatty acids and glycerol
- Fatty acids transporter to liver
Fate of fatty acids in ketoacidosis
Ketones synthesis occurs in the Liver Fatty acids enter mitochondria Fatty acids oxidised to acetyl-CoA Either enter Krebs cycle generate ATP Generate ketones (Acetone, Acetoacetate, beta-hydroxybutyrate) FFA, cholesterol
