Modelling of protein breakdown during critical illness

Modellering af proteinnedbrydelse under kritisk sygdom

Houlberg, Kasper Aarup ; Evald, Mette

4. term

Biomedical Engineering and Informatics, Master

2015

2015-06-03

76

Tab af muskelmasse er et stort problem for kritisk syge patienter på intensivafdelinger, fordi det kan give langvarige helbredsproblemer, længere indlæggelser og højere dødelighed efter udskrivelse. En vigtig årsag er en hypermetabolsk respons på sygdommen, hvor kroppen forbruger mere energi og nedbryder muskelprotein. Proteinrig ernæring kan dæmpe, men ikke forhindre, dette tab. Nitrogenbalance er længe blevet brugt som et indirekte mål for proteintab, men metoden overser dele af den samlede proteinnedbrydelse under kritisk sygdom. Der findes heller ikke en etableret metode til at beregne det enkelte individs muskeltab over en intensivindlæggelse. Dette projekt havde derfor tre mål: 1) at forstå den fysiologi, der ligger bag metabolsk stress hos kritisk syge og dens effekt på proteinnedbrydelse, 2) at indsamle kliniske data, der afspejler stressresponsen, herunder muskelproteolyse, og 3) at bruge denne viden og data til at definere en model, der kan beskrive metabolsk stress gennem indlæggelsesforløbet. Stressresponsen kan deles i en hypometabolsk ebb-fase, en hypermetabolsk flow-fase og en rekonvalescensfase. I flow-fasen stiger energibehovet, og muskler nedbrydes for at levere byggesten til glukoneogenese, hvor aminosyrer, lactat og glycerol omdannes til glukose, som cellerne kan bruge til energi. Data blev hentet fra den kliniske MIMIC II-database. Herfra blev 123 patienter med i alt 134 indlæggelser inkluderet. Visse stressparametre kunne udtrækkes, men ikke alle, for eksempel cortisol. Patienternes energiforbrug (REE, resting energy expenditure) blev estimeret med prædiktionsligninger baseret på patientspecifikke data. På grund af begrænset datatilgængelighed blev projektets modelmål justeret: Der blev opstillet en fysiologisk kompartmentmodel, der beskriver, hvordan aminosyrer fra proteinnedbrydelse bruges til glukoneogenese hos kritisk syge. Fremtidigt arbejde bør fokusere på tidsopløste målinger af metabolsk stress og muskelnedbrydelse. Særligt kombinationen af stresshormoner, især cortisol, med mål for proteinnedbrydelse vil være værdifuld for videre modellering.

Loss of muscle mass is a major problem for critically ill patients in intensive care, leading to long-term health issues, longer hospital stays, and higher mortality after discharge. A key driver is a hypermetabolic response to illness, where the body uses more energy and breaks down muscle protein. High-protein nutrition can reduce, but not prevent, this loss. Nitrogen balance has long been used as an indirect measure of protein loss, but it misses parts of the overall proteolysis seen in critical illness. There is also no established method to estimate an individual’s muscle loss over an ICU stay. This project therefore had three aims: 1) to understand the physiology behind metabolic stress in critical illness and its impact on protein breakdown, 2) to collect clinical data that represent the stress response, including muscle proteolysis, and 3) to use this knowledge and data to define a model that describes metabolic stress throughout the ICU admission. The stress response typically includes a hypometabolic ebb phase, a hypermetabolic flow phase, and a recovery phase. In the flow phase, energy needs rise and muscles are broken down to supply substrates for gluconeogenesis, where amino acids, lactate, and glycerol are converted into glucose for cellular energy. Data were drawn from the MIMIC II clinical database. A total of 123 patients with 134 ICU stays were included. Some stress parameters could be extracted, but not all—for example, cortisol was unavailable. Patients’ energy expenditure (REE, resting energy expenditure) was estimated using predictive equations based on patient-specific variables. Due to limited data, the modeling goal was adjusted: a physiological compartment model was developed to describe how amino acids from protein breakdown are used for gluconeogenesis in critically ill patients. Future work should collect time-resolved data on metabolic stress and muscle breakdown. In particular, combining stress hormone measurements, especially cortisol, with measures of protein breakdown would greatly strengthen modeling efforts.

[This abstract was generated with the help of AI]

Proteinnedbrydelse

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