ABSTRACT
References ......................................................................................................................................601
Critical illness following major trauma, sepsis/infection, burns, or other severe inflammatory process induces complex hormonal alterations, with subsequent impact on endocrine, metabolic, nutritional, and immunological functions. The gravity of related endocrine responses may vary according to such factors as the magnitude and duration of catabolic stress, baseline nutritional status, age, and various pharmacological agents. The primary alterations with endocrine processes observed during periods of acute stress include, but are not limited to:
glands (i.e., growth hormone, cortisol, catecholamines, and glucagons) • Stimulation of cytokine release by immune cells and other cell types (interleukins [IL-1,
IL-6], tumor necrosis factor [TNF]) • Alterations with thyroid hormone metabolism and release • Diminished gonadal steroid secretion • Reductions in insulinlike growth factor-1 (IGF-1) and IGF binding protein-3 levels • Resistance of peripheral tissue to anabolic hormones (i.e., insulin, growth hormone [GH],
and IGF-1)
The cytokine-and counterregulatory hormone-induced acceleration of protein breakdown and the diminished secretion and tissue sensitivity to endogenous anabolic agents are major contributing factors to the protein-catabolic response observed during periods of acute illness.1 The purpose of this chapter is to discuss the potential endocrine and metabolic alterations that may result from tissue injury or stress and the principal endogenous mediators involved. A more thorough examination of the metabolic manifestations of critical illness is made elsewhere.2-4
The metabolic response to critical illness or injury serves to increase the availability of critical macronutrient substrates necessary for survival (amino acids, glucose, free fatty acids [FFAs]), control the immune response, and alter anabolic and reproductive functions.5,6 A sympathoadrenal release of glucagon, cortisol, catecholamines, and GH is induced by the stress response.6 Such activity is stimulated by factors including hemorrhage, volume depletion, alterations in body temperature, acid-base alterations, oxygen and nutrient substrate availability, pain or other emotional stressors, infection, and trauma-induced inflammation or tissue damage. Hormonally induced alterations in response to critical illness may contribute to various physical indices of patient morbidity, including muscle atrophy, infection, gastrointestinal deterioration, and tissue injury.2,3,5,6
The various phases following tissue injury or stress are best exemplified following trauma, in which a clearly defined initiation point is evident. The ebb (early) phase is the initial metabolic response that occurs within the first 24 to 36 hours following injury. This period is characterized by profound volume depletion, reduced cardiac output, and subsequent alterations in tissue perfusion. Oxygen consumption and metabolic rate are reduced, and there may also be a simultaneous reduction in body temperature. Nitrogen loss due to protein catabolism is minor at this time. The increased rates of lipolysis and gluconeogenesis allow for a high production of FFAs and endogenous glucose to serve as primary fuel sources for vital organs, including cardiac muscle and brain. This phase is also characterized by increased serum counterregulatory hormone levels concomitant with lower insulin levels.2-4,6
Following the acute resuscitation period, if full recovery does not arise, the patient may make a transition to a more chronic stage (“flow phase”), which may be prolonged for several days to weeks, depending on the severity of illness and the response to clinical interventions.7 This period is marked by increases in metabolic rate, catabolism, oxygen consumption, cardiac output, and possibly fever.7 Rates of protein synthesis are accelerated, secondary to enhanced production of acute-phase proteins by the liver.7 However, protein degradation surpasses the synthetic capacity, leading to a net negative nitrogen balance and erosion of lean body mass.1,8 The degree of nitrogen loss in the critically ill patient is directly proportional to the level of physiological stress, regardless of nutritional support interventions.2,3
role.1,3,4,9 Research has shown the release of catecholamines by the adrenal glands to play a central role in the maintenance of homeostasis after various insults.4 Investigations with denervated heart preparations have provided evidence to support the ability of catecholamines to induce tachycardia in response to such stressors as cold, pain, oxygen deprivation, or muscle stimulations.4 Others have demonstrated the importance of neural pathways in the initiation of the stress response. Studies have found a reduction in adrenal steroid production in animals that sustained burn injuries in denervated limbs, following medulla oblongata transection or transection of the spinal cord proximal to the site of injury.4 However, obstruction of neural pathways during the flow phase of critical illness was not shown to alter whole-body thermogenesis.4 Thus, neural pathways appear to play a role in the initiation of the stress response, rather than its perseverance.
