FYI - Severe Injury
(This discussion is based largely on material from E. A. Newsholme & A. R. Leach (1983) Biochemistry for the Medical Sciences, John Wiley, NY.)
We've looked at fasting as an example to demonstrate metabolic integration at both the pathway and organ level. As a second example we can follow up with a situation which mimics aspects of starvation with some major differences - severe injury.
A complicating aspect of severe injury is that it often leads to anorexia, and if surgery is involved in response to the injury, then the patient fasts beforehand. In either case fasting is the result, so we would expect to see a fasting response.
In fact much of the response seen in severe injury mimics fasting. Thus serum values of a variety of substances are similar:
- Lactate increases
- Free fatty acids increase
- Ketone bodies increase
- There is a negative nitrogen balance (nitrogen is released as proteins and amino acids are broken down).
But some important differences also occur:
- Metabolic rate increases
- Serum glucose increases (e.g. to about 7 mM compared to about 5mM fed and 3.5 mM fasting)
- Rapid protein loss occurs
These changes are likely due to hormonal changes. Specifically catacholamines, glucocorticoids and glucagon are increased, while insulin decreases. This would be expected to lead to the increased glucose concentration in blood via gluconeogenesis and glycogenolysis in the liver, while increased cortisol can cause increased protein breakdown.
The massive breakdown of protein in severe injury appears maladaptive, and medications are often used to reduce general protein degradation in clinical situations. So why would evolution lead to such a situation? It may simply be that the system has been stressed past its recovery point, where in nature the chances of survival are minimal, so there has been no adaptation. After all it is a common occurrence for normally adaptive responses to disease (e.g. high fever to aid in overcoming infection) to be the actual cause of death under severe conditions.