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De Potentieel Beschermende Rol van Vetweefsel Tijdens Kritieke Ziekte

Critical illness is the disease state in which the function of one or more organ is hampered to the extent that the patient will die shortly, unless intensive medical support is administered. Although the majority of patients are discharged from the intensive care unit within 5 days, at least30% remain dependent on intensive care for a longer period. Mortality in these prolonged critically ill patients still remains around 20% worldwide. Critically ill patients requiring prolonged intensive care display a feeding-resistant hyper catabolism characterized by profound protein loss. Muscle tissue functions as a great protein reservoir providing amino acids for gluconeogenesis and synthesis of acute-phase proteins in the liver. Muscles provide substrate to reparative cells for healing, especially in the acute phaseof critical illness when food intake and nutrient absorption are compromised. Consequently, when critical illness is prolonged, the profound decrease of lean body mass evokes weakness, delays weaning from mechanicalventilation, and impairs rehabilitation. At the same time, paradoxically, adipose tissue is preserved. Moreover, aggressive nutritional support does not prevent protein loss in spite of fat gain. The primary metabolic role of adipose tissue is to store excess energy as triglycerides. This excess energy mainly originates from circulating lipids, which are taken up by adipocytes. A much smallerpart of the stored triglycerides in adipocytes is de novo synthesized from circulating carbohydrates through lipogenesis. Critically ill patients suffer from dyslipidemia and hyperglycemia. The severity of these alterations is associated with adverse outcome. Moreover, elevated circulating glucose and triglycerides levels can aggravate vital organ function during critical illness.

We hypothesized that adipose tissue during prolonged critical illness could respond to increased levels of circulating toxic metabolites by increasing its storage properties. We studied this hypothesis by elucidating the nutritional impact on adipogenesis and macrophage accumulation during critical illness in human adipsoe tissue bioppsies and in our mouse model of critical illness. Secondly, we investigated wehter pre-existing obesity induces a different resposne to critical illness, again in human adipose tissue biopsies and in our mouse model of critical illness.

Datum:1 okt 2009 →  19 dec 2013
Trefwoorden:critical illness, adipose tissue, kritieke ziekte
Disciplines:Anesthesiologie, Intensieve zorgen en spoedgevallen
Project type:PhD project