Post on 28-Mar-2015
Acute phase proteins and other Acute phase proteins and other systemic responses to inflammationsystemic responses to inflammation
Dr Donald C McMillan,Dr Donald C McMillan,University Department of Surgery,University Department of Surgery,Royal Infirmary, Glasgow, UK. Royal Infirmary, Glasgow, UK.
SYSTEMIC INFLAMMATION
MODS
SYSTEMIC INFLAMMATION
MODS
Shock/
hypoxia
Pancreatitis
BurnBurn
Infection
Infective diseases Non-infective diseases
Trauma
Ebb and flow phases of CuthbertsonEbb and flow phases of Cuthbertson
Ebb Flow Phase Pre-resuscitation phase Recovery phasePoor tissue perfusion Normal tissue perfusionHypometabolic HypermetabolicDecreased energy expenditure Increased energy expenditure Increased glucocorticoids Normal glucocorticoidsIncreased catecholamines Normal catecholaminesLow insulin Increased insulinNormal glucose production Increased glucose productionMild protein breakdown Profound protein breakdown
Cuthbertson et al. 1930
The metabolic response to injuryThe metabolic response to injury
Pathophysiological changes of thePathophysiological changes of thesystemic inflammatory responsesystemic inflammatory response
Gabay and Kushner, NEJM, 1999
Neuroendocrine changesNeuroendocrine changesFever, somnolence, fatigue and anorexiaFever, somnolence, fatigue and anorexiaIncreased adrenal secretion of cortisol, adrenaline and glucagonIncreased adrenal secretion of cortisol, adrenaline and glucagon
Haematopoietic changesHaematopoietic changesAnaemia Anaemia LeucocytosisLeucocytosisThrombocytosisThrombocytosis
Metabolic changesMetabolic changesLoss of muscle and negative nitrogen balanceLoss of muscle and negative nitrogen balanceIncreased LipolysisIncreased LipolysisTrace metal sequestrationTrace metal sequestrationDiuresisDiuresis
Hepatic changesHepatic changesIncreased blood flowIncreased blood flowIncreased acute phase protein productionIncreased acute phase protein production
Mediators of the metabolic responseMediators of the metabolic responseto injuryto injury
Cuthberston (1930) Increased protein breakdown and REECuthberston (1930) Increased protein breakdown and REE
Selye (1940’s) Corticosteroids proposed as mediatorSelye (1940’s) Corticosteroids proposed as mediator
Allison (1960’s) Insulin resistance proposed as mediatorAllison (1960’s) Insulin resistance proposed as mediator
Cytokines (1980’s) TNF, Il-1, Il-6 proposed as mediatorsCytokines (1980’s) TNF, Il-1, Il-6 proposed as mediators
Adipokines (1990’s) Leptin, adiponectin, ghrelin?Adipokines (1990’s) Leptin, adiponectin, ghrelin?
Hormonal Metabolic Chemical
Catecholamines REE pH
Glucagon Hyperglycemia Prostanoids
Corticosterioids Ketoacidosis Leukotrienes
Insulin Resistance Uremia Cytokines
Mediators of the metabolic responseMediators of the metabolic responseto injuryto injury
SIRS SIRS (Systemic Inflammatory Response Syndrome)(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 PaCO2 <32 mmHg.
– White blood cells > 12,000 cells/ml or < 4,000
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;20:864-874.
Acute phase proteins andAcute phase proteins andthe systemic inflammatory responsethe systemic inflammatory response
Gabay and Kushner, 1999
day 6day 5day 4day 3day 2day 1pre op
C-r
eact
ive
pro
tein
(m
g/l)
300
200
100
0
Crozier et al., 2004
C-reactive protein in patients undergoingC-reactive protein in patients undergoing curative surgery for colorectal cancercurative surgery for colorectal cancer
-20 0 20 40 60 80
Starvation
Elective Surgery
Sepsis
Closed Head Injury
Multitrauma
Major Burn
Skeletal Trauma
% Above Usual Requirement
Resting energy expenditure in injuryResting energy expenditure in injury
-40 -20 0 20 40 60
GI (Crohn's)
Lung (COPD)
Liver Failure
Acute Renal
Acute Renal
Cancer
Resting energy expenditure in diseaseResting energy expenditure in disease
% Above Usual Requirement
Resting energy expenditure increased by 10-50%to support increased metabolic workload
An additional allowance is added for activity20 % if confined to bed30 % if ambulatory
Energy Requirements Following Surgery
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
Loss of Lean Body Mass
Lean body mass= body cell massmetabolically active compartment
Irreversible at some pointcritical mass
• 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 Protein requirements are increased to accommodate:accommodate:
Operative measures to reduce protein lossOperative measures to reduce protein lossin surgical injuryin surgical injury
Minimise the inflammatory stimulusSurgical techniquesAnaesthesiaControl of sepsisEnvironmental temperatureControl of pain and anxiety
Nutritional interventionIf oral intake less than 60% of energy and proteinrequirements by 10 days
Activation of white blood cells, fibroblasts, endothelial cells
Release of Il-6, Il-1, TNF, Interferons, growth factors
CIRCULATION
C-reactive protein Zinc RetinolAlbumin Iron Alpha-tocopherolHaemoglobin Copper Carotenoids
QUALITY OF LIFE
Fatigue Performance status
INFL
AM
MA
TO
RY
PR
OC
ESS
Injury and the systemic inflammatory responseInjury and the systemic inflammatory response
WHOLE BODY
Resting energy expenditure Weight loss Body cell Mass
HEALING
The systemic inflammatory response plays an important rolein determining protein loss in acute and chronic disease.
Acute phase proteins in particular C-reactive protein andalbumin are useful in quantifying the magnitude of this responseand both are associated with poor outcome
Conclusions