- The magnitude of the metabolic response depends on the degree of trauma and the concomitant contributory factors such as drugs, sepsis and underlying systematic disease. The response will also depend on the age and sex of the patient, the underlying nutritional state, the timing of treatment and its type and effectiveness. In general, the more severe the injury (i.e. the greater the degree of tissue damage), the greater the metabolic response.
- The metabolic response seems to be less aggressive in children and the elderly and in the premenopausal woman. Starvation and nutritional depletion also modify the response. Patients with poor nutritional status have a reduced metabolic response to trauma compared to well-nourished patients.
- Burns cause a relatively greater response than other injuries of comparable extent probably because of the propensity for greater continued volume depletion and heat loss.
- Whenever possible, it is critical to try to prevent or reduce the magnitude of the initial insult, because by doing so it may be possible to reduce the nature of the response, which while generally protective may be harmful. Thus aggressive resuscitation, control of pain and temperature, and adequate fluid and nutritional provision are critical.
- The precipitating factors can broadly be divided into:
Hypovolaemia
- Decrease in circulating volume of blood
- Increase in alimentary loss of fluid
- Loss of interstitial volume
- Extracellular fluid shift
Afferent impulses
Wound factors: inflammatory and cellular
- Eicosanoids
- Prostanoids
- Leucotrienes
- Macrophages
- Interleukin-1 (IL-1)
- Proteolysis inducing factor (PIF)
- Platelet activating factor
Toxins/sepsis
Oxygen free radicals
Hypovolaemia
- It is said that hypovolaemia, specifically involving tissue hypoperfusion is the most potent precipitator of the metabolic response. Hypovolaemia can also be due to external losses, internal shifts of extracellular fluids and changes in plasma osmolality. However, the most common cause is blood loss secondary to surgery or traumatic injury.
Table 2. ATLS classification of shock
Class of shock
|
% Blood loss
|
Volume
|
Class I
|
15%
|
<750 ml
|
Class II
|
30%
|
750–1500 ml
|
Class III
|
40%
|
2000 ml
|
Class IV
|
>40%
|
>2000 ml
|
- Class III or class IV shock is severe, and unless treated as a matter of urgency, will make the situation much worse.
- The hypovolaemia will stimulate catecholamines which in turn trigger the neuroendocrine response. This plays an important role in volume and electrolyte conservation and protein, fat and carbohydrate catabolism. Early fluid and electrolyte replacement, and parenteral or enteral surgical nutrition administering amino acids to injured patients losing nitrogen at an accelerated rate; and fat and carbohydrates to counter caloric deficits may modify the response significantly. However, the availability of the methods should not distract the surgeon from his primary responsibility of adequate resuscitation.
Afferent impulses
- Hormonal responses are initiated by pain and anxiety. The metabolic response may be modified by administration of adequate analgesia, which may be parenteral, enteral, regional or local. Somatic blockade may need to be accompanied by autonomic blockade, in order to minimise, or abolish the metabolic response.
Wound factors
- Endogenous factors prolong or even exacerbate the surgical insult, despite the fact that the primary cause can be treated well. Tissue injury activates a specific response, along two pathways:
- Inflammatory (humoral) pathway
- Cellular pathway
- Uncontrolled activation of endogenous inflammatory mediators and cells may contribute to this syndrome.
- Both humoral and cell-derived activation products play a role in the pathophysiology of organ dysfunction. It is important, therefore, to monitor post-traumatic biochemical and immunological abnormalities whenever possible.
Immune response: inflammatory pathway
- The inflammatory mediators of injury have been implicated in the induction of membrane dysfunction.
Eicosanoids
- These compounds, derived from eicosapolyenoic fatty acids, comprise the prostanoids and leucotrienes (LTs). Eicosanoids are synthesised from arachidonic acid which has been synthesised from phospholipids of damaged cell walls, white blood cells and platelets, by the action of phospholipase A2. The leucotrienes and prostanoids derived from the arachidonic acid cascade play an important role.
Prostanoids
- Cyclo-oxygenase converts arachidonic acid to prostanoids, the precursors of prostaglandin (PG), prostacyclins (PGI) and thromboxanes (TX). The term prostaglandins is used loosely to include all prostanoids.
- The prostanoids (prostaglandins of the E and F series, prostacyclin (PGI2) and thromboxane synthesised from arachidonic acid by cyclo-oxygenase (in TXA2), endothelial cells, white cells and platelets, not only cause vasoconstriction (TXA2 and PGF1), but also vasodilatation (PGI2, PGE1 and PGE2). TXA2 activates and aggregates platelets and white cells, and PGI2 and PGE1 inhibit white cells and platelets.
Leucotrienes
- Lipoxygenase, derived from white cells and macrophages, converts arachidonic acid to leucotrienes (LTB4, LTC4 and LTD4). The leucotrienes (LTB4, LTC4 and LTD4) cause vasoconstriction, increased capillary permeability and bronchoconstriction.
Immune response: cellular pathway
- There are a number of phagocytic cells (neutrophils, eosinophils and macrophages), but the most important of these are the polymorphonuclear leucocytes and the macrophages. Normal phagocytosis commences with chemotaxis, which is the primary activation of the metabolic response, via the activation of complement.
- The classic pathway of complement activation involves an interaction between the initial antibody and the initial trimer of complement components C1, C4 and C2. In the classic pathway, this interaction then cleaves the complement products C3 and C5 via proteolysis to produce the very powerful chemotactic factors C3a and C5a (anaphylotoxins).
- The so-called alternative pathway seems to be the main route following trauma. It is activated by properdin, and proteins D or B, to activate C 3 convertase, which generates the anaphylotoxins C3a and C5a. Its activation appears to be the earliest trigger for activating the cellular system, and is responsible for aggregation of neutrophils and activation of basophils, mast cells and platelets to secrete histamine and serotonin, which alter vascular permeability and are vasoactive. In trauma patients, the serum C3 level is inversely correlated with the injury severity score (ISS). Measurement of C3a is superior because the other products are more rapidly cleared from the circulation. The C3a/C3 ratio has been shown to correlate positively with outcome in patients after septic shock.
- The short-lived fragments of the complement cascade, C3a and C5a , stimulate macrophages to secrete interleukin-l (IL-1) and its active circulating cleavage product proteolysis-inducing factor (PIF). These cause proteolysis and lipolysis with fever. IL-1 activates T4 helper cells to produce IL-2, which enhances cell-mediated immunity. IL-1 and PIF are potent mediators stimulating cells of the liver, bone marrow, spleen and lymph nodes to produce acute-phase proteins which include complement, fibrinogen, a2-macroglobulin and other proteins required for defence mechanisms.
- Monocytes can produce plasminogen activator, which can adsorb to fibrin to produce plasmin. Thrombin generation is important due to its stimulatory properties on endothelial cells.
- Activation of factor XII (Hageman factor A) stimulates kallikrein to produce bradikinin from bradykininogen, which also affects capillary permeability and vaso-activity. A combination of these reactions causes the inflammatory response.
Toxins
- Endotoxin is a lipopolysaccaride component of bacterial cell walls. Endotoxin causes vascular margination and sequestration of leucocytes, particularly in the capillary bed. At high doses, granulocyte destruction is seen. A major effect of endotoxin, particularly at the level of the hepatocyte may be to liberate tumour necrosis factor (TNF) in the macrophages.
- Toxins derived from necrotic tissue or bacteria, either directly or via activation of complement system, stimulate platelets, mast cells and basophils to secrete histamine serotonin.
Oxygen free radicals
- Oxygen radical formation by white cells is a normal host defence mechanism. Changes after injury may lead to excessive production of oxygen free radicals, with deleterious effects on organ function.