Major trauma can provoke a neuroendocrine response that is characterized by activation of the sympathetic-adrenomedullary system and by stimulation of neurohypophysial neurones in the hypothalamus, resulting in alterations in synthesis and secretion of various pituitary hormones and subsequent changes in secretion of adrenal, pancreatic and thyroid hormones. This complex response has been well described after a variety of physical injuries, including long-bone fractures, multiple injuries and burns. The neuroendocrine response to physical injury is accompanied by and possibly causally linked to a number of metabolic and immunological disturbances in patients. These include negative nitrogen balance as a consequence of increased protein breakdown, changes in thermoregulation, metabolic acidosis and immunosuppression as evidenced by the high mortality caused by sepsis in traumatized patients. The neuroendocrine response to physical injury is thought to be initiated by three main factors: emotionality caused by perception, fluid loss and tissue damage. The temporal integration of a sequence of neuroendocrine and metabolic reactions has led to a division of the response to injury into two phases, which have been named the ‘ebb’ and ‘flow’ phase (Cuthbertson, 1930; Frayn, 1986).
The ebb phase, which lasts up to 12-24 h after injury, represents a coordinated response by the brain, and is characterized by mobilization of energy stores together with apparent restraints on energy utilization. Early studies have reported that the ebb phase is characterized by a fall in metabolic heat production. However, subsequent studies, in particular in humans, have demonstrated that heat production is usually raised soon after injury, with a magnitude dependent on the type and severity of the insult (Little, 1988).
The flow phase or catabolic phase is characterized by a rise in metabolic rate, roughly coincident with an increase in urinary nitrogen secretion, which lasts up to 10 days after the injury. This phase of the response resembles a state that has been denoted the acute phase response, which is known to be largely regulated by cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) (Dinarello, 1984; Kaplan et al, 1989; Heinrich et al, 1990).
The main emphasis of this chapter is to review the nature and cause of changes in hormone concentrations that occur after physical injuries. A brief description of the possible effects is added, to promote a more adequate understanding of the regulatory role of the neurohormonal response to injury.