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Acute phase proteins and other systemic responses to inflammation Dr Donald C McMillan, University Department of Surgery, Royal Infirmary, Glasgow, UK.

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Presentation on theme: "Acute phase proteins and other systemic responses to inflammation Dr Donald C McMillan, University Department of Surgery, Royal Infirmary, Glasgow, UK."— Presentation transcript:

1 Acute phase proteins and other systemic responses to inflammation Dr Donald C McMillan, University Department of Surgery, Royal Infirmary, Glasgow, UK.

2 SYSTEMIC INFLAMMATION MODS SYSTEMIC INFLAMMATION MODS Shock/ hypoxia Pancreatitis Burn Infection Infective diseases Non-infective diseases Trauma

3 Ebb and flow phases of Cuthbertson EbbFlow Phase Pre-resuscitation phaseRecovery phase Poor tissue perfusionNormal tissue perfusion HypometabolicHypermetabolic Decreased energy expenditureIncreased energy expenditure Increased glucocorticoidsNormal glucocorticoids Increased catecholaminesNormal catecholamines Low insulinIncreased insulin Normal glucose productionIncreased glucose production Mild protein breakdownProfound protein breakdown

4 Cuthbertson et al The metabolic response to injury

5 Pathophysiological changes of the systemic inflammatory response Gabay and Kushner, NEJM, 1999 Neuroendocrine changes Fever, somnolence, fatigue and anorexia Increased adrenal secretion of cortisol, adrenaline and glucagon Haematopoietic changes AnaemiaLeucocytosisThrombocytosis Metabolic changes Loss of muscle and negative nitrogen balance Increased Lipolysis Trace metal sequestration Diuresis Hepatic changes Increased blood flow Increased acute phase protein production

6 Mediators of the metabolic response to injury Cuthberston (1930) Increased protein breakdown and REE Selye (1940s) Corticosteroids proposed as mediator Allison (1960s) Insulin resistance proposed as mediator Cytokines (1980s) TNF, Il-1, Il-6 proposed as mediators Adipokines (1990s) Leptin, adiponectin, ghrelin?

7 Mediators of the metabolic response to injury

8 SIRS (Systemic Inflammatory Response Syndrome) The systemic response to a wide range of stresses. –Temperature >38°C (100.4°) or <36°C (96.8°F). –Heart rate >90 beats/min. –Respiratory rate >20 breaths/min or PaCO 2 <32 mmHg. –White blood cells > 12,000 cells/ml or 10% immature (band) forms. Note –Two or more of the following must be present. –These changes should be represent acute alterations from baseline in the absence of other known cause for the abnormalities. American College of Chest Physicians/Society of Critical Care Medicine Consensus. Crit Care Med. 1992;20:

9 Acute phase proteins and the systemic inflammatory response Gabay and Kushner, 1999

10 Crozier et al., 2004 C-reactive protein in patients undergoing curative surgery for colorectal cancer curative surgery for colorectal cancer

11

12 Starvation Elective Surgery Sepsis Closed Head Injury Multitrauma Major Burn Skeletal Trauma % Above Usual Requirement Resting energy expenditure in injury

13 Resting energy expenditure in disease % Above Usual Requirement

14 Resting energy expenditure increased by 10-50% to support increased metabolic workload An additional allowance is added for activity 20 % if confined to bed 30 % if ambulatory Energy Requirements Following Surgery

15 If there are insufficient protein reserves there is: decreased wound healing decreased immune response defective gut-mucosal barrier decreased mobility/ respiratory effort Surgery: Protein & Amino Acid Metabolism

16 Loss of Lean Body Mass Lean body mass= body cell mass metabolically active compartment Irreversible at some point critical mass

17 Immune response Increased metabolic activity Replacement of damaged cells Replacement of protein losses –perspiration, blood, exudates, renal, intestinal – if anorexia accompanies fever/infection – by muscle proteolysis Protein requirements are increased to accommodate:

18 Operative measures to reduce protein loss in surgical injury Minimise the inflammatory stimulus Surgical techniques Anaesthesia Control of sepsis Environmental temperature Control of pain and anxiety Nutritional intervention If oral intake less than 60% of energy and protein requirements by 10 days

19 Activation of white blood cells, fibroblasts, endothelial cells Release of Il-6, Il-1, TNF, Interferons, growth factors CIRCULATION C-reactive proteinZincRetinol Albumin IronAlpha-tocopherol HaemoglobinCopperCarotenoids QUALITY OF LIFE FatiguePerformance status INFLAMMATORY PROCESS Injury and the systemic inflammatory response WHOLE BODY Resting energy expenditureWeight lossBody cell Mass HEALING

20 The systemic inflammatory response plays an important role in determining protein loss in acute and chronic disease. Acute phase proteins in particular C-reactive protein and albumin are useful in quantifying the magnitude of this response and both are associated with poor outcome Conclusions


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