1. Hormonal Response

The abnormal hormonal environment activated by stress is in large part responsible for the metabolic changes.  There is an increase in the gluconeogenesis, insulin resistance hormones and an increase in catabolic and decrease in anabolic hormones.

2. Inflammatory Response

Local and systemic inflammations are typically seen, especially after trauma or infection.  Whenever there is a wound, inflammation is present.  The pro-inflammatory cytokines will increase energy demands as well as protein denaturation leading to catabolism.  Inflammatory mediators such as oxidants and proteases will denature protein resulting in a net catabolism.  The term “auto-destructive inflammation” is used to describe the process.

Inflammatory Response to a Burn Injury:

• Mediator induced cell damage

• Oxidant induced protein degradation
• Cytokine induced hypermetabolism and catabolism

• Pyrogen release elevating Temperature

3. Metabolic Response

The metabolic changes which occur markedly alter the bodies processing of macronutrients.  After injury, an intense stimulus to liver gluconeogenesis is caused by the abnormal environment and a rapid breakdown of body protein (catabolism) occurs for use as carbohydrate substrate with the source being lean mass.  The amino acids are released mainly as alanine for liver glucose formation and glutamine for use as fuel by the gut and for production of the endogenous antioxidant glutathione found in all tissues.  Protein is not spared and 24-30% of consumed protein is used for energy production.  Fat stores are inadequately utilized.

With the increased metabolism, the normal calorie requirements increase one and one half to two times.  Because of the altered metabolism, the normal compensatory mechanisms initiated with starvation are absent.  The process is no longer substrate sensitive; i.e. giving nutrients does not decrease the metabolic response.  The overall demand for glucose is increased so that at least 50 percent of the non-protein calorie requirement needs to be provided by carbohydrate to spare the protein stores from breakdown.  Otherwise muscle catabolism increases further to provide the necessary substrate for gluconeogenesis.  Also exogenous amino acids will be used for calories if insufficient carbohydrate is present.  The large energy store in fat is not effectively used.

"Stress Response"  (Hormonal & Inflammation Components)

• Increased metabolic rate and increasing energy demands
• Inefficient use of substrate through recycling
• Increased catabolism
• Decreased anabolism
• Increased body temperature

Figure 13:

4. Combines Stress & Starvation

A  “stressed” burn patient can no longer adapt to lack of nutrition like a starved patient when there is a protection of the lean mass and fat is the major fuel.  The presence of starvation is therefore much more deleterious in the post-burn patient.  Weight loss and lean mass loss is very rapid.

In general, the “stressed” patient should not be starved for more than 48 hours before nutritional support is started in order to decrease the progressive morbidity of lean mass loss.

5. Stress & Sepsis

The response to severe injury, infection and inflammation is a further magnification of the stress response.  Increases in circulating inflammatory mediators, particularly macrophage derived products, as well as marked sustained increases in the anti-insulin and catabolic hormones (catechols, cortisol, glucagons, and growth hormone) are present.  Although insulin levels are also increased, the anti-insulin activity appears to be dominant.

An entire spectrum of abnormalities can be seen due to degrees of the manifestation of the host “stress response” initiated by a burn insult and resulting in mediator release and perpetuated by a systemic release of stress hormones.  Oxidants and other neutrophils products released by cytokines such as tumor necrosis factor, produce direct cell injury while the abnormally high levels of the catecholamines, glucagons and cortisol lead to the metabolic abnormalities, which will also produce cell injury.  The degree of response depends on the degree of injury or infection, age, body composition, and, the patient’s preprogrammed genetic response to an insult.  If uncontrolled, the stress response can progress to multiple-organ dysfunction caused by an excessive loss of body protein as well as direct cell injury by oxidants and other mediators.  The stress response becomes auto-destructive and acute cannibalism (catabolism for fuel) occurs with rapid loss of lean body mass.

This self-perpetuating process causes two critical dilemmas.  The first is that in order for the cycle to be broken, the initiating focus must be eliminated and the inflammatory response must abate.  Second, once the mediator factory of the body’s macrophage and neutrophils pool has been primed.  Even a modest second insult can reactive a massive mediator release and cause cell destruction.  Controlling the degree of ongoing injury requires both controlling the host response and at the same time supporting the metabolic needs.

6. Multi-system Organ Failure

With progression of the septic process or inflammation, organ failure results.  The liver plays a central role in this process.  Continued exposure of the liver to bacteria, or bacterial byproducts results in cellular dysfunction.  In addition, the cells in tissues are altered so that carbohydrate is less effectively utilized.  Insulin infusion at this later stage may not improve glucose utilization.  The total amino acid oxidation is increased as increased amounts of branched chain amino acids are utilized directly for energy, with up to 30 percent of the calories being generated from protein.  Increased hepatic cholestasis with fat deposition occurs particularly if carbohydrate calories in excess of utilization are given.  Glucose calories then account for 35 to 40 percent of the total calories.  The liver is no longer capable of clearing and deaminating the increased levels of circulatory amino acids resulting from the increased breakdown, especially the aromatic amino acids.  The latter, when increased in plasma, can act as false neurotransmitters, producing lethargy and central nervous system depression.  The respiratory quotient during this process is 0.8 to 0.85, indicating that some fat (35 to 40 percent of the total calories) is being used for fuel.

If the process continues, liver dysfunction progresses to the point that liver protein synthesis decreases.  The effect of the increase in visceral protein breakdown is now accentuated by the decrease in liver protein synthesis.  Net catabolism increases while inadequate energy is produced at the cell level to sustain cell integrity, and progressive organ failure ensues.