Critically ill patients are in a catabolic state, characterized by three major metabolic
changes. First, there is an increased protein turnover with enhanced hepatic protein
synthesis and muscle protein breakdown. Second, during critical illness there is
increased lipolysis, or the breakdown of triglycerides to free fatty acids (FFA) and glycerol.
And third, insulin resistance causes hyperglycemia due to ongoing endogenous
glucose production (glycogenolysis and gluconeogenesis) and blunted peripheral
uptake. These metabolic derangements are caused by various endogenous and exogenous
triggers, including increased inflammatory cytokines (Tumor Necrosis Factor
α, interleukin-1, interleukin-6, and interleukin-8), catecholamines and glucocorticoids,
all in which insulin resistance plays a central role.This response to injury is universal
and has been beneficial all through evolution at the acute onset of severe disease or
trauma. However, modern medicine has improved survival rate and critical illness has
become a process which lasts not just mere hours but can last for days or even weeks.
Early last century Sir David P. Cuthbertson described the short initial hypometabolic
“ebb” phase, followed by the prolonged hypermetabolic “flow” phase during adult
critical illness. Persistent glucose overload and breakdown of skeletal muscle and
adipose tissue releasing large amounts of amino acids and FFA are the result. Unfortunately,
although plasma substrate levels may be increased, their availability to
peripheral tissues may be blunted (because of factors such as insulin resistance and
inhibition of lipoprotein lipase), while plasma levels of other substrates (e.g. specific
amino acids, cholesterol) may be insufficient to meet metabolic demands. As a
result, these metabolic changes, beneficial in the initial phase from a teleological viewpoint,
become detrimental during prolonged critical illness.
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