Patient description: The patient is a 60-year-old Spanish man presenting with shortness of breath about a day before. The symptoms began acutely and progressively worsened. He is a known case of COPD since 2 years ago. The spirometry revealed post-bronchodilator FEV1/FVC = 60% of predicted values. He smokes 20 cigarette per day. His past medical history is remarkable for BPH and he is using Flomax for that. His family history is positive for HTN in his brother. His medication includes Duo-Neb inhaled q4 hr PRN, Vit D3 1000 units per day and Flomax for his PBH. He is an obese man who is acutely ill but oriented and conscious. The vital signs are as bellow: BP: 135/80 RR: 25/min HR: 75 bpm BMI: 40 O2sat: 90%

Clinical trial eligibility criteria: eligible ages (years): 16.0-999.0,  Sepsis Critical Illness Group 1: healthy control patients Patients undergoing elective total hip replacement will be eligible for enrollment in Group 1 after written informed consent has been obtained. Only 1 blood sample and 1 fat and muscle biopsy will be taken intra-operatively Group 2: non-septic, critically ill patients Patients requiring intensive care within 48 hours of admission to hospital from home, for a non-septic/non-inflammatory pathology will be eligible for enrollment in the study after informed agreement has been obtained from the closest family member (see Consent below). At enrolment, Group 2 patients must have received mechanical ventilation commencing within 48 hours of admission to intensive care, should be likely to require mechanical ventilation for at least 48 hours, and must not fulfil the 2001 International Sepsis Definition Conference for severe sepsis or septic shock Group 3: patients with severe sepsis or septic shock Patients requiring intensive care within 48 hours of admission to hospital from home, and evidence of severe sepsis (organ dysfunction due to infection) or septic shock as defined by the 2001 International Sepsis Definition Conference will be eligible for enrollment in the study after informed agreement has been obtained from their next-of-kin. Patients with underlying chronic liver disease are excluded from this group, and will be enrolled separately into Group 4. Group 4: patients with severe sepsis and underlying chronic liver disease Patients requiring intensive care admission, with underlying Child-Pugh Class A or B, biopsy-proven liver cirrhosis, within 24 h of the onset of severe sepsis (organ dysfunction due to infection) or septic shock as defined by the 2001 International Sepsis Definition Conference criteria), will be eligible for enrollment in the study after informed agreement has been obtained from their next-of-kin  Age <18 years Child-Pugh Class C liver disease Chronic dialysis-dependent renal failure Hepatitis B or C infection Immunosuppression (e.g. haematological malignancy, neutropenia, HIV infection) Immunosuppressive drug therapy within past 6 months Patient receiving oral or IV steroid therapy for greater than 1 week, within 6 months prior to ICU admission Muscle biopsy contraindicated in presence of coagulopathy (INR >2, platelet count < 30,000)* Next-of-kin declines agreement / patient declines consent Patient receiving thyroid hormone therapy prior to ICU admission *This does not enrolment into the study, particularly in the case of Group 4 patients who frequently develop a coagulopathy as part of their underlying liver dysfunction