Proefschrift Kerklaan

Chapter 1

Characteristics of the acute phase of critical illness The acute phase of critical illness in children is characterised by the requirement of (escalating) vital organ support. The concomitant stress response, initiated by activation of an inflammatory cytokine cascade and the central nervous system, is aimed at surviving critical illness. A conceptual overview of the neuro-endocrine, metabolic and immunologic alterations is depicted in Figure 1.

Figure 1. Conceptual overview of the different phases of critical illness with corresponding neuro- endocrine, immunologic and metabolic changes EGP, endogenous glucose production; PT, protein turnover; GH, growth hormone; rT3, reverse triiodothyronine; REE, resting energy expenditure; MPS, muscle protein synthesis; IGF-1, insulin-like growth factor; T3, triiodothyronine; counter-regulatory hormones are cortisol, catecholamines and glucagon Neuro-endocrine response Despite activation of the hypothalamic-pituitary axis to release the anterior pituitary hormones corticotrophin (ACTH), thyroid stimulating hormone (TSH) and growth hormone, concentrations of most peripheral effector hormones, such as triiodothyronine (T3, active thyroid hormone) and insulin-like growth factor (IGF-1) are low due to inactivation or target organ resistance 17-19 . In absence of adrenal insufficiency, levels of cortisol rise substantially, mainly due to reduced metabolism in liver and kidneys 20,21 .

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